At Home Laser Treatment for Arthritis and Joint Pain with the Kineon Move+
Reducing joint pain and inflammation with laser therapy
New things are possible for your joint health, as the next generation of ‘at home’ light therapy devices hits the market.
Could the Move+ from Kineon heal your knee/joint pain? Yes, it certainly could. Read on for more…
Laser therapy for chronic joint pain - does it work?
The answer hasn’t always been yes. Amazon and eBay are awash with low quality imitators and ‘cold laser’ clinics have popped up around the globe with very mixed reviews.
We’ll spare you too many details, as we know you’re in search of something that actually works (hang tight - we won’t disappoint!)
In short - there are many pitfalls facing new users of laser therapy devices.
Three Issues with At Home Laser Treatment Devices
Firstly, most at home treatment options claiming to be ‘lasers’ (watch out for 'low level’ or ‘low intensity’ or ‘cold’ terminology) are simply using LEDs and are not truly a laser therapy device. One ‘tell’ is that light power will be rated in the milliwatts (mW) rather than watts. These devices will never get light deep into your joint (necessary for stimulating stem cell activity and oxygenating blood!).
Secondly, nearly all of the lower cost devices are not effectively calibrated to penetrate joint tissues at depth. This is related to the first point (power), but there’s more to consider - light needs to be focused in a column not a spray to penetrate into the joint. LEDs cannot do this - you need an authentic laser emitter (with true light amplification).
Third, price point. We’ve reviewed all of the at home laser treatment devices we could find. Most of them do not have enough power, nor do they focus light in a column appropriately. The few that do cost several thousand to tens of thousands of dollars. This is why the laser treatment options that actually work have historically only been used on athletes or available at expensive clinics.
Choosing Effective At Home Laser Therapy for Joint Pain and Arthritis
These three issues do not mean that at home laser treatment for joint pain is a bust! They simply mean that you need assistance in choosing an at home laser therapy for arthritis pain - and that is why the team at Longevity Blog have done the hard work for you!
The aches and pains of arthritis and joint pain in general are usually driven by one key factor - inflammation.
We review the basics on how to keep your cartilage healthy and your joints pain free in part one of our interview series with Kineon.
We highly recommend you check it out!
We are always tracking the latest developments in longevity technology (which is why you should subscribe to our monthly updates!).
A key trend we discovered in this process is that the proliferation of laser devices in aircraft, cars, robotics means the price point for high quality lasers has recently begun to fall very quickly.
Kineon, led by pioneering CEO Forrest Smith, were very quick to realise the opportunity to bring low cost, high quality laser treatment for joint pain to the market. With the Move+ launching just months ago, we knew we’d found a game changing device for at home treatment of joint pain. They have cracked the trifecta of problems in laser quality, device calibration and price point.
And as their devices have begun shipping to users worldwide, self-experimenters everywhere are validating the effectiveness of this device. Today, we’re going to discuss how you can get your hands on one and hear from Forrest directly on how to self-experiment at home to know if laser treatment for joint pain will work for you.
Kineon’s Move+ - a light therapy device which relieves joint pain safely and quickly by stimulating factors which support healthy joint cartilage.
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Kineon, we are please to offer a 10% off coupon code for the Move+, exclusive to our readership
Use the code “longevitymove+“
This interview was conducted in June 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Be Sure to Read Part One of the Interview with Kineon Here!
Laser Treatment for Arthritis in Hands, Knees, Joints
Longevity Blog (LB):
Coming back to the beta testers you mentioned - using the Move+ on yourself and testing how it might work for you is what this audience loves to do. It's one of the things that we focus on.
Often our Founder Nick is the guinea pig, but increasingly our audience are participating and sharing the results with us.
The Move+ seems to offer great opportunities for self experimentation. Let’s consider a reader who has, say, a shoulder or a knee issue and is interested to try the Move+
Let's talk about how they would do a self-experiment. Let’s hear some details - how long they should run it for, how often they should treat the joint and what they could effectively measure before and after?
Self-Experimenting with the Kineon Move+ for Joint Pain
Forrest Smith (FS): We've run a number of different tests and found a couple that are really interesting. I’ll share the most accessible one.
One way to check if the device is working through all of the mechanisms that we've discussed is using a blood flow restriction cuff where you can reduce the blood flow to the affected limb to essentially zero. Then, you remove the cuff and let the blood reperfuse.
You measure how long this takes, first recording a baseline measurement. Then you test again after several weeks of treatment. This is an extremely powerful test in a couple of ways.
One - the faster your tissue reperfuses, the healthier you are from a cardiovascular standpoint. Second - in most instances, any previous injury (such as an old ACL tear) will result in slower reperfusion of the blood into the affected leg.
You should be able to see a difference after just one month of treatment. Then you can retest the numbers. We’ve done this across many beta testers and what we're seeing is that the microvasculature is improving extremely well.
We might see a 20% differential between left and right leg and pull it up to within a 5% differential after only a month of treatment.
At Home Laser Treatment for Joint Pain - How Long Does it Take?
LB: You mentioned one month of treatment. Tell us about what the treatment protocol during that one month period.
FS: The protocol that has been most effective for testers to date is five minutes of treatment on the actual joint, and then five minutes upstream and five minutes downstream. You can then increase that treatment period over time to a maximum of around 10 to 12 minutes for each.
LB: Would you do this every day? And you just mentioned the reader should do this for a month? What happens if you go longer?
“five minutes of treatment on the actual joint, and then five minutes upstream and five minutes downstream”
FS: Yes, everyday, and you can absolutely treat for longer. One month is just the starting point.
LB: It also sounds like you can perform this treatment while sitting still. You can use the Move+ while watching Netflix or playing a video game. It sounds like it's pretty easy to use and it doesn't take a lot of time?
FS: That was one of our core goals as a company, and I harp on it quite a bit with our team. We wanted to build a device that is making the most substantial change possible in the quality of life of the highest number of people we can.
To achieve that, we need to remove inconvenience and make the device as functional as possible so customers can use it on a daily basis. I typically use my Move+ during a breathing and meditation session in the morning.
If you can find something that you do habitually, whether it's a cup of coffee in the morning, or whether it's a routine that you have before going to bed - use the Move+ then. You can use it when you’re moving or sitting down and even when you’re completely focused on something else. It's battery powered, it's wearable, and it's quite comfortable relative to anything else on the market.
The Cost of Laser Treatment for Knee Pain
LB: We are looking forward to trying the Move+ out!
Tell us about how we can get our hands on a device. How much does it cost to get an at home laster therapy device for knee pain and arthritis? And where can you find it?
FS: Right now we are selling for $397. We are also going to offer your readers a discount, in the spirit of self-experimentation!
Get 10% off the Move+
Use the code “longevitymove+“
LB: We are very excited about this 10% discount, which brings the price down to $357USD.
Let’s discuss the price point you just mentioned, for some $400-$500 USD might feel quite expensive. However, there is a story here, and that price point actually represents a real technological advancement.
Similar devices which have been used in a clinical setting cost $15,000 or more. The $400-$500 price point Kineon is offering reflects how you’ve really innovated to deliver this device at such a low price.
FS: Absolutely. It really reflects back to our core mission. We knew we were going to have to get the cost way down. This has to be a device that people can afford to have in their homes, and that they can use conveniently and frequently, or is not going to impact their life the way that it should.
LB: We love that mission!
Where Laser Therapy for Joint Pain is Headed Next
LB: As we move forward and wrap up this interview - we want to end with two things in mind. A forward looking view of where the longevity industry is headed and secondly, what you're doing for your own health and longevity
Let’s start with looking into the longevity future and let's narrow it down in terms of the scope of photobiomodulation light therapy. Where is that going in the next decades specific to health and longevity? What are we going to see?
“with the application of cheaper lasers...we are soon going to be able to track specific molecules in your blood”
FS: We've thought long and hard about this and we see some really good ways to be able to impact people's lives and quality of life in the next 3 to 5 years that haven't been available up until now
We think optical sensors paired with light therapy emitters is going to create many new opportunities. This is the next generation of what you might see on a Garmin watch right now. The green LEDs on the back of your Garmin watch which make for a not so accurate heart rate monitor.
With the application of cheaper lasers and better sensors with some machine learning will be a very powerful combination. We're going to be able to track many new physiological characteristics and even specific molecules in your blood.
We have this capability at the research/hospital level and they will be in your home in the next 3 to 5 years. Kineon plans to be in that space as well, so hopefully we can talk more about this soon!
The Surprising Connection Between Lasers and Gut Health
LB: Brilliant, that's really exciting. You’ve mentioned a few areas where light therapy is producing impressive and unexpected outcomes for cardiovascular health, brain health, but one other you mentioned in the lead up to the interview was gut health.
Tell us, briefly, how there could be a relationship between lasers and gut health?
FS: There's fundamental clinical research into this now using machine learning and mapping bacterial populations in your gut, and even determining the health of that bacterial population.
When you apply photobiomodulation positive outcomes result. For example, different bacterial populations generate different waste materials based on what they are consuming. Early testing in clinical trials with photobiomodulation appears to support healthier gut bacteria.
With our dosing models along with a digital signal processing and machine learning team, we are exploring applications for our light therapy devices in the gut. Watch this space!
LB: That's exciting. If you need a guinea pig, we are all ears.
Forrest Smith CEO at Kineon’s Longevity Strategy
LB: Onto our second question. Share a few of the top things you do when looking out for your own longevity. Tell us about your longevity strategy. Give us one or two things that you're doing each day to look after yourself.
FS: I would say carb cycling and fasting are what I’ve been onto for the longest. I've seen ongoing great results and it's very simple. Fasting and carb cycling has been amazing from a health standpoint.
The Kineon Move+ in action, tipping the balance back in favour of cartilage regrowth & join healing.
Obviously, the light therapy treatments have been helpful for getting myself back into training after injuries. And then there’s daily meditation. I have been doing this for the last five or six years. Pairing that with breathing has been super powerful.
LB: And with that daily meditation, we can now think about adding lasers to the mix! This is a great illustration of what's possible in the longevity feature.
Thank you for joining us today Forrest. There's a lot more to talk about, but for now we're going to head off and play around with the Move+. Our thanks to your team for making it possible to have such a power device in the homes!
FS: Fantastic. Thanks so much. I really appreciate the opportunity to be interviewed on Longevity Blog.
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Regrowing Knee Cartilage and Restoring Joint Health Naturally. An Interview with Kineon CEO Forrest Smith - Part 1
Can you regrow cartilage?
New things are possible for your joint health, as the next generation of ‘at home’ light therapy devices hits the market.
Could the Move+ from Kineon heal your knee/joint pain? Yes, it certainly could. Read on for more…
Can you regrow cartilage in the knee without surgery? Can you regrow cartilage at all?
This is a very popular question on Google, but unfortunately, if you’re searching for this answer - you don’t get many promising solutions.
Some will tell you - No, you cannot regrow cartilage, full stop. Others list some promising prescription drugs that might work, some day maybe.
Well, that doesn’t lead to much hope for sufferers of osteoarthritis, or those who are asking - Can you regrow cartilage in the knee without surgery?
People looking for answers to questions like these might feel like they are chasing a medical miracle. They might even experience feelings of hopelessness or despair.
Well, guess what, it’s 2022 and longevity technology development is moving faster than ever. Rejuvenating technologies that make living a younger, healthier life for longer are rapidly emerging.
So you’ll have to excuse Google for being a bit behind the times - but there’s a new kid on the block, and it just may mean that it is now possible to regrow cartilage in the knee naturally.
And it doesn’t stop there - but let’s not get too ahead of ourselves. We need to cover a few basics, up front.
Can you reverse cartilage damage?
At left, a healthy knee joint. At right, an arthritic joint with cartilage degradation. Note the widespread inflammation. Image source: Wikipedia
Let’s start off with some important details about cartilage, beginning with several common myths about cartilage.
Osteoarthritis myths
Arthritis is simple “wear & tear”
Arthritis doesn’t heal.
Cartilage doesn’t regrow
Exercise makes it worse
None of the above are true, yet most people believe them.
This does not take away from the pain that many millions of people around the world experience due to joint degradation. That is 100% real.
In fact, joint health is a major longevity issue, and looking after your joints is an essential part of your longevity strategy.
Patients with severe pain due to osteoarthritis stop walking and moving regularly. They often suffer from accompanying illnesses such as depression and cardiovascular disease.
And when it comes to longevity, being able to move your body is absolutely essential to your quality of life. Walking speed, calf strength, aerobic fitness - the list of ‘longevity metrics’ related to joint health goes on - you need to be looking after you body’s ability to move to stay healthy and live long.
Cartilage Regeneration is about Balance
To better understand cartilage regrowth, we need to stop thinking about cartilage as a finite resource that you use up, and instead see it as part of a balancing act.
In our interview today, we’re introducing you to a new partner company Kineon and their CEO and Co-Founder Forrest Smith, who had this to say:
As you age cartilage may grow more slowly, but it never really stops. What happens instead is an imbalance, typically in joints, of growth of new cartilage versus cartilage degradation. Especially if you have long term chronic inflammation, or osteoarthritis. It’s this osteoarthritis that causes the degradation of the cartilage.
By reducing inflammation, you're reducing the degradation rate of the cartilage. And that means your body can build that cartilage back faster. So it is actually on both sides of the equation, it is a balancing act.
So if you are suffering from a lack of cartilage in the knee or another joint (like the hip or shoulder), you need to reconsider your own cartilage balancing act.
And here is where it gets exciting - and where new technology is now available to help you with both sides of the equation.
Kineon’s Move+ is a brand new product which leverages decades of research on light therapy, recent advancements in the cost and quality of lasers and a new, very driven team of experts who have created a device designed to help you reduce inflammation and boost cartilage regrowth.
If you’re keeping track, that means you’re seeing improvements on, as Forrest said above, “both sides of the equation”.
Kineon MOVE+, Does it Work?
To date, early testers of this device have been completely ‘wowed’ by the effects they’ve seen (scroll down on the Kineon homepage to see testimonial videos) on their levels of pain and restoration of function in joints which have plagued them for years and even decades.
Kineon’s Move+ - a light therapy device which relieves joint pain safely and quickly by stimulating factors which support healthy joint cartilage.
They are a very promising sign that it may be time to re-think the answer to the question - Can you regrow cartilage in the knee? It’s simply not a hard “No” anymore.
And for those who have long suffered from joint pain, there may at last be hope again.
But, as is our usual preamble - at Longevity Blog, our job is to put such claims to the test! We’re here to help you get your hands on a device at a discount and guide you through testing before & after to quantify the results yourself.
We also ask the tough questions of the founders and lead scientists at longevity tech companies, to help you cut through the marketing and onto the results.
So, our fellow joint health enthusiasts, let’s hear more from Forrest, CEO at Kineon…
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Kineon, we are please to offer a 10% off coupon code for the Move+, exclusive to our readership
Use the code “longevitymove+” at checkout to save 10%!
This interview was conducted in June 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Longevity Blog (LB):
Forrest, welcome to Longevity Blog! It's one of the most common health questions on Google, full stop.
So I'd like to start by asking - can you regrow cartilage? The answer to this question is a very important one for our longevity. In particular, people are interested in regrowing cartilage in the knee without surgery.
What's your answer to this question?
Forrest Smith (FS):
Thanks for having me! As you age cartilage may grow more slowly, but it never really stops. What happens instead is an imbalance, typically in joints, of growth of new cartilage versus cartilage degradation. Especially if you have long term chronic inflammation, or osteoarthritis. It’s this osteoarthritis that causes the degradation of the cartilage.
By reducing inflammation, you're reducing the degradation rate of the cartilage. And that means your body can build that cartilage back faster. So it is actually on both sides of the equation, it is a balancing act.
There are two primary ways to improve cartilage growth, which are well established in the medical literature. The first is increasing the rate of collagen type 2, which is a building block for the extracellular matrix that is the framework or the infrastructure for the cartilage to regrow.
The second is by boosting mesenchymal stem cells activity, which differentiate into building blocks for cartilage.
Interestingly, when you apply light therapy, these stem cells are encouraged to create the infrastructure for building cartilage.
YES, YOU CAN REGROW CARTILAGE
LB: Thank you for the detailed answer there. What we are hearing is a “yes” to this question - can you regrow cartilage. But the answer, as with many things in biology, is not that simple. The key concept here is that of balance.
By minimising the degrading your cartilage in your joints, and boosting the things that rebuild the cartilage in those joint, we can have positive cartilage growth.
Your company Kineon is has built some very interesting technology for improving this balance in the favour of cartilage growth. But to understand it, we’re goint to need to introduce a few new terms to the audience.
One of them is photobiomodulation, which we'll jump into in some detail coming up. The other one you just mentioned is mesenchymal stem cells. A lot of our readership knows about stem cells, stem cell therapy is popular in longevity.
Let's talk in a little bit more detail about mesenchymal stem cells. Tell us about them and how they are involved in cartilage growth and repair.
LIGHT THERAPY FOR JOINT REPAIR
FS: Mesenchymal stem cells can turn into almost any other other type of cell. They're a very useful building block for your body. You generate them primarily from your bone marrow, deep within the bone.
What we are seeing in the medical literature is that by using light therapy, mesenchymal stem cells are more likely to differentiate into cell types which support cartilage and bone growth.
“when you apply light therapy, these stem cells are encouraged to create the infrastructure for building cartilage”
LB: Great, thank you. And so what we're hearing to summarise, is that in terms of answering the question, Can we regrow cartilage in the joints? Or can we regrow cartilage in the knee? - we need to think about the balance.
So we should focus on reducing the amount of factors that are tearing down cartilage and increasing the number of factors that are building it back up.
Mesenchymal stem cells, which are produced in the bone marrow that differentiate into bone and into the cartilage are important to support and boost cartilage regrowth and repair.
The Kineon Move+ in action, tipping the balance back in favour of cartilage regrowth & join healing.
Let’s now come back to the research that you're mentioning and our next new terms - light therapy or photobiomodulation. Tell us a little bit about what this term means?
FS: Photobiomodulation is a bit of a blanket term. Originally, when light therapy was being researched, there were a couple of terms that were used by the scientific community.
The medical and scientific research community can get a little bit divisive about terms. It sounds extraordinarily technical, relatively what it actually is, but it's basically putting the lasers, LEDs and everything using light to interact with biology under one roof.
Photobiomodulation - How Does it Work?
LB: Okay, so it's an all encompassing term photobiomodulation. What we find most interesting about the term is the ‘bio’ part. The medical literature you are referring to has shown in various ways that the application of light to the body is impacting how it works at a cellular level.
Can you comment on this? In particular, the interaction between stem cells and joint cartilage?
Image credit: quitemindfm
FS: This is a really good segue into some of the fundamental mechanisms behind how light therapy works.
The research up until recently had indicated that the primary mechanism of function for the photobiomodulation was the light impacting molecules in the phospholipid bilayer of your mitochondria.
Effectively light therapy promotes a more effective and more efficient use of energy in your mitochondria. This is one of the primary drivers of the outcomes
But it's not the only one, and more recently there’s been a few more mechanisms of action discovered…
LB: We are excited to hear about these Forrest, but before we do, it is important to emphasise that it is very well established that light interacts with our biology.
One of the primary mechanisms for doing so is by stimulating mitochondrial energy production, as you’ve just mentioned.
The Move+ from Kineon uses both lasers and LEDs to direct light therapy into the joint safely and effectively.
This is why there have been many ‘red-light therapy’ products entering the longevity and wellness marketplace over the past decade. Most of our audience will be familiar with these.
LED light type therapies that their favourite biohacker on instagram might stand in front of, or perhaps shining red light on your face to boost collagen production, or maybe even using red light therapy on your shoulder or back to relieve aches or pains.
Kineon’s Move+ - A Next Generation Light Therapy Device
What we want to emphasise is that the light therapy product Kineon has brought to market - the Move+ - stands out from these types of light therapy for several key reasons.
Not only is it a therapeutic device modelled after units used in the clinical setting, but it is also using both lasers and LEDs at the same time, to stimulate these ‘multiple mechanisms’ of action, not just mitochondria.
Let’s look deeper into the differentiators here. Firstly, talk to us about how you're using two types of light therapy in the device.
Our Founder Nick is self-experimenting with the Move+ over the next two months, to see if it can help him recovery from a triathlon over-training injury. Be sure to subscribe to hear about the results!
FS: One of the problems in the literature, which is only recently improving (over the last 3-5 years), is that medical researchers didn't really understand the technical side of the equation (e.g. light coherence, wavelength, intensity) and at the same time, the technical side didn't understand the medical physiology.
What you ended up with was a number of papers that were reporting the data that was easiest for them to report and so you had inconsistent metrics measuring the optical parameters of the light.
We've spent a lot of time dialling into what the technical and physiological terminology and metrics mean. Essentially the Rosetta Stone for all of these earlier meta medical trials. This has allowed us to interpret the many different medical research trials and know the ‘dosage’ of light for a given application.
What is Dual Therapy? Laser and LEDs
LB: Bringing it back to the Move+ product, you’ve incorporated a dual therapy including both LEDs and lasers in the same device. You’ve implemented this unique design after comprehensively reviewing and translating results from across widespread research literature, which support this ‘dual therapy’ approach.
FS: That's exactly right. The most important part of the problem is getting the dosage of light correct. For this, you have to know the amount of photons that you're putting out and how they're being put out.
LEDs emit light in essentially a spray, just an open spray in all directions, it's called a lambertian emission pattern. They're typically packaged, or bonded, into a cup, which contains them to a 120 degree emission pattern. But what we've done is we've actually pulled those LEDs even tighter with our own proprietary optics down to 30 degrees. This ensures the right level of penetration.
We're using LEDs for our deep red at 650 nanometers and our lasers are a near infrared wavelength at 808nm, which is the most proven and the optimal balance the photobiomodulation impacts we are targeting
“we know exactly how deep we’re dosing and how much light is going into the tissue, targeting microvascular level effects”
LB: This is a great opportunity to mention a few more of these mechanisms of action, specific to these wavelengths and the LED therapy.
Light therapy boost circulation
FS: There's also impacts for haemoglobin. When this red and infrared light hits haemoglobin, it strips out nitric oxide. Nitric oxide has some really powerful impacts on your physiology. It dilates blood vessels, providing more blood to tissue in areas where it's become stagnant. Here it is important to target a certain depth into the tissue.
With the Move+ we know exactly how deep we're dosing and how much light is going into the tissue, targeting these kind of microvascular level effects. The LEDs spread of light opens up the microvasculature. Then the penetration from the lasers and the infrared deep into the internal tissues provide a really powerful combination.
LB: That's the dual therapy combination right there. We really want to talk more about the lasers but before we do, first let’s cover one more topic on the LEDs and red light. Explain to us a bit more about how this specific LED wavelength is opening up microvasculature and improving blood flow and therefore tissue repair.
FS: Having the right wavelengths of red and infrared light at the right depth where your microvascular sits around your joints brings fresh blood because stripping out nitric oxide dilates those blood vessels. This means blood flow increases in the area.
LB: Can you give us an example of this effect? Some evidence as to why this is important for healing?
Injury Can Drive Cartilage Loss
FS: One of the things that you see with chronic tissue damage in joints happens typically after some kind of traumatic joint tissue damage, like an ACL tear, or meniscal tear, or even sprains. The inflammation from this injury doesn't just stay contained to the joint, it actually also damages the microvasculature around the joint as well.
Are you an athlete? Looking for other ways to recover more effectively. You might really like what we have discovered about a new longevity supplement - Urolithin A. Read about it here!
There was a study of 3000 NFL players where 50% had an ACL tear and 50% did not (control). In the group with the ACL tear, the tissue temperature in their damaged leg quadricep was two degrees lower than the tissue damage in the healthy quad. Surprisingly they also had a 50% increased risk of severe cardiovascular disease afterwards!
What this data is showing us is that, not only is the tissue damaged in the joint, there is also long term inflammation generated throughout your body and even into your cardiovascular system. This means damage from an endothelial standpoint, stiffer veins and arteries and long term negative impacts in overall health.
So, when you're treating joints with light therapy, you're not just treating the joints, you’re also improving the upstream and downstream microvascular. So that you can actually stop having that trickle of inflammation that adds up over time.
LB: In our background research on cartilage degradation, we found that previous injury was one of the major causes of cartilage degradation. The development of lesions (areas of acute damage) in the cartilage or even damage to a ligament often sets up the degradation of cartilage years later. Severe loss of cartilage can limit mobility, and this is where we really get into the longevity part of the picture
What we're hearing about the right type of red light LED treatment is that this opening up of the microvasculature is getting fresh blood flow into these areas and reducing inflammation. But we’ve not yet heard about cartilage or internal joint repair, is that where the lasers come in?
Laser Light Therapy Penetrates Deep into the Joint
FS: The laser allows treatment of the synovial fluid and the tissue inside the joint directly, which is not something that you're really going to be able to do with the LEDs. If you have an LED only device, it's definitely better than nothing. But it's not penetrating the internal tissues.
Lasers emit as a column of light and work really well for dosing internal tissues. Our light propagation models have shown us that with the Move+ laser, the internal tissue is receiving the correct levels of dosage. It would take an unthinkable amount of LEDs to reach that level of penetration.
LB: The laser allows for deeper penetration into the joint as a whole, but it is both of these light emitting technologies (LEDs and lasers) together that help rebuild healthy cartilage.
But there's a key aspect of this that you've just touched on - biphasic dose response. That term sounds a little bit complicated and might be intimidating to the reader, but essentially what it means is that there's too much of a good thing and there's too little of a good thing.
There's something in the middle that we want to hit with the Move+ treatment protocol. Can you first tell us what a biphasic dose response is, and then, secondly, how you've used that information to get the right amount of light into the joint for healing/repair?
FS: I think you've done a great job of explaining it. There is essentially a curve where the amount of dosage delivered is on one axis the results are on the other axis.
As the amount of dose increases, it's going up a hill until there's an optimal point at the top. Then it goes back down that hill. We've spent a lot of time on our light propagation models so that we can justify the correct dosage from the Move+ device.
Early Testers of the Move+ are Making Impressive Claims
LB: What your team is doing differently is that you’re thinking specifically about joints and merging multiple types of light therapy technology with very specific calibration to have very specific healing effects in that joint. With the right dosage, you’re increasing blood flow, improving synovial fluid health and increasing the activity of the mesenchymal stem cells.
Ed says knee pain was greatly limiting his life, but the Move+ gave him his life back. “It just transformed my knees”
You've had some pretty interesting success with early testers of this device and have some very convincing testimonial videos. Do we have enough information to know you've gotten these dosage models right?
FS: We have enough information to know that we've done better than any of the other light therapy offerings out there. But I think we still have work to do.
One of the things we've seen from our early testing with beta users, that I think will speak to your audience from a longevity standpoint very well, is that when we're treating large tissue masses (e.g. the leg), we're not just seeing the nitric oxide rise in that area, we're seeing it all over the body.
This means your serum levels of nitric oxide are getting much higher and the benefits of that stay in your system for you 24 to 72 hours. This has a really positive effect on your endothelial tissue and keeping that healthy is one of the best things you can do from a cardiovascular standpoint. That's also particularly true with your brain.
We're seeing very high levels of nitric oxide crossing over to the brain, which improves vascular health in your brain.
Would the Move+ Work for You? There’s only one way to find out…
LB: These are some very interesting systemic results! We’ll be following up on them.
Coming back to the beta testers - using the Move+ on yourself and testing how it might work for you is what this audience loves to do. It's one of the things that we focus on.
Often I'm the guinea pig, but increasingly others are doing the same and sharing the results with us. The Move+ seems to offer great opportunities for self experimentation. Let’s consider a reader who has, say, a shoulder or a knee issue and is interested to try the Move+. …
INTERVIEW Part 2 AVAILABLE HERE!
Get 10% off the Move+
Use the code “longevitymove+" to save 10%!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Longevity: Fasting, Diet, Sleep, Stress - How to Personalise Your Approach
Longevity: Fasting, Diet, Sleep and Stress
Nick and Dr. Robert Lufkin MD dig into the ‘secrets’ of longevity. You can find the full video here.
Understanding how to positively influence your longevity is complicated and at times overwhelming!
Demystifying longevity and simplifying the steps you can take to make improvements to your healthspan (and someday soon, perhaps lifespan) is what Longevity Blog is all about!
Today, we hit upon three major topics in longevity - fasting, diet, sleep & stress in our with Dr Robert Lufkin, MD of Health Longevity Secrets.
How to Fast for Longevity
Fasting is one of the more recent major health trends. And like many health fads, it comes in hot and with plenty of miracle claims on how it cures all forms of ailments.
Analysing the benefits of fasting for your longevity and how you might approach fasting for longevity purposes is a challenging topic area with no ‘straight answer’.
Calorie Restriction and Longevity
Here’s what we know. Calorie restriction (eating slightly fewer calories than your body requires) over a lifetime improves healthspan and lifespan in many animal models, including rodents and even primates (who are closely related to humans).
However, there are no longitudinal studies on fasting which can demonstrate this is the case in humans.
Long-term strict calorie restriction has its advocates in the longevity health space. And quite a spritely bunch they are!
But to date, they are placing their bets on a very challenging type of fasting, which when done inappropriately can actually lead to early death (the opposite of what you want!) in some cases, and which has little to no robust scientific data specific to human longevity or lifespan.
Weight Management and Longevity
We love the fasting app Zero! It’s a great way to track your fasts and join a community of others looking out for their best health interests. Plus its totally free!
One thing that we do know for certain, is that eating too many calories (more than your activity level requires) over a long period of time is associated with many chronic health conditions.
Why? Because it leads to being overweight, even obese, and increases systemic inflammation.
It even increases your biological age.
If you want to improve your health outcomes, you should maintain a healthy weight.
Through the lens of longevity, this makes fasting is a valuable tool. One that can you can use to reduce your weight to a more optimal level & reduce age-related disease risk.
For some insights on the types of fasting you can use to accomplish this, checkout Nick’s discussion with Dr. Lufkin at ~33:40 (or the transcript below) in our YouTube interview!
Does sleep increase lifespan? How many years does lack of sleep take off your life?
Getting quality sleep is essential for your health and longevity. How much does sleep affect your healthspan? Well that depends!
It is well established that getting too little quality sleep is very bad for your health, while getting enough quality sleep helps your body heal/recover more effectively.
From a first principles standpoint - we can predict that getting enough quality sleep is certainly very important for your longevity.
How much sleep do you need?
However, the details behind this statement are difficult to pin down. Your personal needs cannot be explained to you in a generalised blog post.
You have to take this matter very much into your own hands, and become an expert in understanding how you sleep best.
Getting ‘enough good sleep’ breaks down into three major components:
Sleep duration (how much you are sleeping)
Sleep quality (how well you are sleeping)
Sleep schedule (how regular your bedtime/waking time are).
Improve your sleep by tracking sleep duration (how much you are sleeping), sleep quality (resting heart-rate, movement) and sleep schedule.
Once you have a baseline (4-6 weeks of data), start experimenting to see what can improve your numbers in these three categories.
How much sleep (duration) you need is very much an individual statistic. And your personal sleep requirements will change according to the demands of your day.
For example, athletes tend to need more sleep so their bodies can recover from their training. If they were to discontinue their intense training, they would need less sleep overall.
Meanwhile, shift workers who have irregular sleep schedules (e.g. nightshift work a few days/week) are known to have much higher age-related disease risks (e.g. cancer, cardiovascular disease).
How to Measure and Improve Your Sleep
Sleep quality has recently become more measurable, which allows you to monitor it over time and get a baseline for what ‘normal sleep’ looks like for you.
Jump ahead in our video interview to ~39:50 (or the transcript below) to hear from our Founder Nick on some tricks for using everyday wearables to establish your sleep quality and how to analyse what helps you sleep better (or worse!).
How Does Stress Affect Longevity / Life Expectancy?
We hear a lot about how damaging stress is to our health and longevity. So much so, it might even be stressing you out!
“Stress” however, is far too generic a term. For example, stress can be good, so long as it does not overwhelm the biological system. Nature has developed robust responses to stress to recover and then become more resilient against a specific stress.
You can self-experiment with stress, just by observing your emotions, feelings & thoughts. To do so, try mindfulness meditation to practice observing your mental state.
Once you build some basic skills, you’ll be able to better notice how the events of your day impact your mental health.
We’ll be bringing you some examples on how to track stress/anxiety and run a self-experiment in future posts.
What you should concern yourself more with is being able to 1) observe your mental health state and 2) identify what triggers poor mental health for you. From there, you experiment with positive changes to your lifestyle, supplement stack and mental adaptation strategies.
Starting with observing your mental health status, our Founder Nick recommends using mindfulness meditation.
Learning to sit with your thoughts, emotions and feelings creates an ability to observe them. Without practicing this, you’ll lack the all important skillset required to know what is stressing you out.
By building an ability to understand and observe your mental health state, you then become enabled do something about what brings on poor mental health and do something about it.
Using a mindful mind, you’ll be able to the self-reflection and self-observation required to become aware of what specific life events are causing you to feel stressed.
Nick is currently running a self-experiment to improve his anxiety levels, as informed by his personalised genetics report from Self-Decode.
From there, you can develop strategies specific to these triggers.
We’re in the progress of using Nick’s personal results from Self-Decode to explore our personalised stress and anxiety supplement recommendations from their platform, to demonstrate how you can do this effectively!
Tune into the YouTube interview to hear more from Nick on this topic, at ~43:40 (or read the transcript below!).
This is part two of our transcription of an October 2020 interview between Dr. Lufkin and our Founder Nick.
It is in excerpt format, to highlight key points of the discussion with basic edits made for purposes of clarity and correctness. Timestamps are approximate.
Is fasting good for longevity?
Robert Lufkin (RL) at 33:40
What about diet? Fasting, we hear so much stuff about that, and longevity, what's your what's your take on on that as as far as influencing longevity?
Nick Engerer (NE) at 34:02
Look, this is this is a fascinating discussion. And once again, when we start talking about diet, we start talking about fasting. We're really getting onto this question of what will work for you and you need to be able to measure before and after…
Fasting refers to many different types of restricting your diet, it might be calorie restriction, eating a fewer number of calories overall, it might be dietary restriction, removing a certain part of your diet. For example, keto diet, the ketogenic diet, it's an extreme example.
It might also be something where you change the times that you're eating, you might only eat in the evening, you might only for a few hours a day or maybe an eight hour window.
And then there's of course the true fast where you go for a few days at a time, with just some water and electrolytes, maybe a multivitamin
I've experimented with all of them. And so I've had to go through that self-experiment and learn for myself what works best for my biology, and do that through testing my bloods, looking at how I feel, what are my energy levels, what is my skin look like?
What Type of Fasting is Right for Your Longevity?
… Coming back to the point, somebody who is extremely overweight, maybe morbidly obese, and really needs to lose some weight - fasting is a powerful tool for that person, they should absolutely consider it … they might be able to go for extended periods of time and not eat and lose incredible amounts of weight
There might be just the average person who needs to lose 20 pounds, and they so they decide they're going to skip breakfast, eat in a smaller window, and make sure they're not overcompensating for missing breakfast by eating more calories at lunch and dinner.
Why Nick Doesn’t (Currently) Fast
… I mentioned earlier that I'm now a triathlete. So I wake up and eat and then I eat again and then I eat again, and then I eat again. And it's because I'm working out two times a day, to adapt my body to be more of an athletic one. I'm convinced that over a decadal timescale, the most important thing that my biology can have is better mitochondria, stronger muscles and adapted body with great angiogenesis and fresh blood vessels, circulating nutrients and clearing waste throughout my body.
There's all these benefits that I cite for why I'm doing this. Now, that means I'm not necessarily getting the benefits of restricting my calories, which we know does provide longevity benefits. Calorie restriction is one of the most powerful tools for actually improving lifespan outcome in primates. And we think that that applies to humans.
But that's not the only knob you can turn to improve your longevity. There's several - so you have to try to pick a longevity strategy and implement what you think's going to work best for you and your biology over the long-term, and put your cards on the table after you place your bets.
I'm going down the exercise route, I'll probably eat less as I get older overall, but now I'm finding that the eating small meals throughout the day is powering exercise, which is making my body stronger, my heart stronger, and leaving me feeling pretty fantastic.
RL at 38:11
What are the other knobs for longevity? We touched on exercise and diet. What other knobs can we turn there?
Using Blood Testing to Choose a Longevity Diet
NE at 38:25
When it comes down to thinking about your biological age there are four important things you can change, diet, exercise, stress and sleep.
We've just talked a bit about diet (fasting) - let me give a further example on how it can be personalised.
Nick’s blood lipids over time, with 3x different diets highlighted.
When I did the ketogenic diet for a year, my cholesterol levels were out of whack. My LDL-C was too high. My particle count for the lipoproteins was too high.
I looked at that data and said - “Look ketogenic diets, not the right thing for me”.
Instead I've come around to eating low amounts of saturated fat, pretty much eliminating dairy, and still eating red meats, fish, chickened balancing that out with eating a lot more plants
That diet has improved my inflammation levels and reduced my LDL-C and my ApoB number (representing the lipoprotein particles counts and their sizes). So that diet is a healthier thing for me.
But that's not necessarily the thing that will be right for everyone. So you have to back that up with blood testing, how you feel and your overall goals.
Eating a diversity of plants is one diet change Nick can back up with a self-experiment. Checkout the details here! You might find GlycanAge biological age tests to be valuable in your own diet optimisation! Use the code ‘longevityblog’ to save 15%!
Sleep and Longevity - What Nick is Tracking
Let’s talk about sleep next. And also, you've done some great experiments on NMN and some other things. If you want to talk about those that that would be interesting as well.
NE at 40:50
Okay, let me tell you what I think about sleep. Sleep is again, highly personalised, like all this stuff is. Some people will hit the hit the hay and just knock right out and sleep through the night. Good on them. I wish I was one of them. I'm not.
In fact, through analysing my own genome, I am in the the 98th percentile for insomnia! So I'm a bit of a thrasher!
I have to really think about my sleep and get on my A game. I've just pretty much eliminated alcohol altogether in my life. But more importantly, if I'm going to have a drink, it's going to be a day drink.
If I have a single beer or wine for dinner, I can already see resting heart rate increases my heart rate variability drops, and as a result I don't sleep as well for the first part of the night till my body clears that out of its system.
Same thing for eating meal too large of a meal late at night, I'll see elevated heart rate for a few hours before it finally comes down.
That increased heart-rate is reducing the amount of recovery that I get from my sleep.
It's fairly in vogue to do sleep tracking, I get a lot of data from the Oura ring. It's has its limitations. I wouldn't say I trust its sleep stage data very much.
But what it does tell me is it tells me how much I'm moving around. It tells me what my heart rate is and measures my heart rate variability, my body temperature.
Just looking at those metrics alone makes it possible to collect data and infer outcomes.
What about Sleep Supplements? Do they work?
I've also then been able to self-experiment with sleep stack supplements.
For example, I was just trying out valerian root. I thought I felt like I was sleeping better, but when I went back and looked at my data, I couldn't see any evidence of that. So I did not add it to my stack.
I've experimented with other sleep related supplements like magnesium L threonate, or Magtein, but that turned my brain on too much. One of the only things I found that works for me was magnesium glycinate. I'll take around 300-400mg as that seems to relax me a bit.
How to Interpret Your Sleep Data for Optimisation
… So for your own personalization, get a format for collecting data, the most important thing in my view, is being able to see movement and heart rate. Your heart rate should drop off fairly quickly and lower out into a nice plateau and then pick up when you wake up.
If you don't see that, if you see the heart rate staying up and you see it spiking throughout the night along with movement - these are signs that you're not sleeping as well as you could.
You can gather that information from a smartwatch. You can gather that stuff from a ring or a whoop band or any other mechanism you want. But being able to then take it and inform your personal longevity strategy is the most important part.
In my office rocking’ these blue light blocking glasses from DoNotAge. 10% off when you use the code ‘longevityblog’.
That means changing one thing at a time, collecting some data and deciding very objectively - did trying that thing improve my sleep yes or no? Do that over and over again until you know what works for you. That's how I would approach sleep.
One last thing - blue light blocking works for me in terms of sleep onset.
Particularly if you got a screen at night or you're in a bright environment. Light control is huge.
So I take all the blue light out of my environment I turn I got LEDs that light up my home and I turned them down to a warm tone and that turned them down to a red light as we're reading go to sleep in the house.
Controlling the lights is really, really important for sleep.
Stress and Longevity
How about stress then? Same type of thing?
NE at 45:05
Stress - we have a proclivity to it in modern society… I actually intentionally live out what we call in “the bush” in Australia - meaning I live in a rural area. Every time I go to the Big Smoke (Sydney), where my company is based and visit with my team, I'm amazed at just how many cars are trying to kill me, the noise that is in my ears, the pollution I'm breathing in, the light that's coming at me all times of the day…
Learning to understand that your body has having stress response to everyday activities… these things have impact on your subconscious and raise your stress level. Being able to notice what increases your stress level and what is causing you to have a stress response… is important to figure out in your in your own subjective awareness.
Meditation and Longevity - Become Aware of What is Stressing You
The most powerful tool for being able to notice this is mindfulness meditation. I've done a lot of meditating in my life. I've done a lot of self reflection, and meditation retreats - all that good stuff. Meditation has become a powerful tool, much like fasting, that I know when I need to use, and has also given me a baseline awareness to be able to see in my own mind, what I'm experiencing, what I'm thinking, what I'm feeling.
That's what you need to do in order to understand stress, because until you can take that step back and observe the things that are making you feel stressed, you won't know what to eliminate.
Once you can see that, then you need to eliminate and control. I'm actually doing a self-experiment with some of my personal results from Self-Decode, exploring the stress and anxiety supplements that have been recommended to me by my genetic reports
Self-experimenting with these supplements is important because the same thing won't work for everyone. A great example - CBD oil makes me feel anxious. I feel good for the first hour and then I feel anxious for the three hours after that. That's not the experience that most people have.
Developing the skills to figure that out for yourself by self experimenting, adding one thing at a time, keeping a journal … That's the way to approach managing stress.
So first - mindfulness to gain perspective, and then (second) try taking things away or adding things in (supplements) to control that stress more effectively.
RL at 47:38
I'm hearing the theme of personalization and being aware of your own body and what works for each of us. It's such an important important message.
What about supplements,? You mentioned a couple like resveratrol or NMN. Anything there you recommend?
…
This interview continues, covering Nick’s multiple self-experiments and his role as an Advisor to DoNotAge.
If you’d like to hear more, you You can watch the rest of this video interview between Dr. Robert Lufkin, MD and our Founder Nick here.
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Nick posts plenty of #Longevity content to Instagram as well, follow him @nickengerer
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
How to use biological age testing kits and build a personalised longevity strategy
What is my biological age?
Nick and Dr. Robert Lufkin MD dig into the ‘secrets’ of longevity. You can find the full video here.
Your biological age can be estimated through a number of different methods. We’ll discuss those in some detail in this post.
What this biological age value is attempting to answer is - how old are you really? Meaning, how old is your body at the cellular level?
Answering this question has only recently become possible.
But one of the challenges is - there are many ways to ‘measure’ it, and not all of them will give you the same answer!
More to the point - can these tests enhance my longevity strategy?
How Do You Measure Biological Age?
Biological age can be ‘measured’ by a blood test or a saliva sample.
Using these samples, certain aspects of the sample are analysed, depending on the test type:
Telomere length (looking at your chromosomes)
Phenotypic age (comparing a compilation of blood tests to your peers)
Epigenetic age (looking how your DNA is expressed by the epigenome)
GlycanAge (reviewing the signalling molecules for inflammation in the body)
How to Calculate Biological Age
This question brings us nicely to our interview subject matter today.
Calculating biological age from the above samples is based on the following process, with widely varying degrees of simplification:
Researchers gathering many thousands to hundreds of thousands of the above samples
Building a model based on the chronological age of the donors + the markers measured
Choosing the risk target of the model (e.g. all cause mortality is most common)
Using the model to review your sample to tell you how hold you ‘look’ compared to your peers, biologically
There are many commercial offerings for doing this, several of which we have reviewed in detail on Longevity Blog (read on for more!).
What Does A Biological Age Value Tell You?
Biological age and longevity is a complicated topic, and it is not easy to sort through marketing hype and make a clear decision on how you want to engage with this relatively new technology.
Thankfully, our friend and colleague Dr Robert Lufkin is looking to make sense of these messages and find the ‘secrets’ often buried in the details.
In his recently launched Health Longevity Secrets show, he’s delivering a new episode/podcast each week interviewing topic areas experts.
On episode 18, he interviewed our Founder Nick, covering a wide range of topics with a distinct focus on biological age (the focus of this post) and also fasting, sleep, stress and diet (the focus of part two of this interview).
We’re bringing you the highlights (hosted on YouTube) of the discussion in excerpt form, where the tables have turned and Longevity Blog the interview subject for a change!
This is a transcription of an October 2020 interview between Dr. Lufkin and our Founder Nick. It is in excerpt format, to highlight key points of the discussion with basic edits made for purposes of clarity and correctness. Timestamps are approximate.
Biological age testing and the Personalised longevity strategy
Robert Lufkin (RL) 1:18
Maybe just to start off - when did you know you wanted to focus on longevity? I mean, you're not that old right now. So what happened?
Nick Engerer (NE) 3:08
I'm 35, but I've always been interested in health as a hobby.. That came through for me in powerful way in my late 20s when I had three important people in my life get cancer in the same year, all in their late 20s.
One of those was my wife - diagnosed with appendix cancer 30 minutes after my son was born through Caesarean section.
Those encounters with mortality really got me thinking at a young age around what can we do to engage with this ever present risk that we have in the background … there's a lot of technologies around to enable proactive screening for health conditions of all types. There's a big trend going on now with proactive healthcare technologies being able to pick up diseases earlier and earlier.
The costs and barriers of those coming down further and further.. those two trends really caught my interest.
building a personalised longevity strategy to simplify complexity
RL at 5:34
We’re all about ‘Sticking Around’, and self-experimenting with the many ways of doing so. Like this self-experiment with NAD booster NMN!
The Longevity Blog, which I love! … I love the motto for it: “Stick around”. That’s good… I look forward to reading and every time
Stepping back, how do you view longevity? What is your concept of longevity?
NE at 6:05
I'm a scientist ... I come to this thinking with a scientific view. I find it really interesting that we have an increasing availability of ways to test and gather data on our own body, and then form a view of how we interact with our health and specifically our longevity with that information.
When I think about longevity as a problem space… there's simply so much that one can do. There's so many pathways… it's simply overwhelming to try to engage with all of them. It's not possible.
How do we really simplify that? I like to think about it in terms of developing a personalised strategy. We’re working to pull together content on Longevity Blog…
I'll give you a specific example about how to think about this…. We can do a number of different exercises to actually personalise your risk profile.
The most simple example is doing a family health questionnaire; what did your grandfather and your grandmother on both sides of your family - what age related diseases did they experience? What about your parents, aunts and uncles?
This is totally free… you can take your doctor and start a discussion. See ahead of time - there's early heart disease in my family, what am I going to do about that? Or there's early onset Alzheimer's in my family. What am I going to do about that?
This simplifies the problem space down to some first actions that you can start to take in targeted ways to engage…
Personalised Longevity Strategy - where to start?
RL at 9:14
That's such a good point Nick. It's one thing to talk about longevity and and do the rapamycin and the resveratrol but we all need to first look at our risk factors because we can boost our longevity …
Giving blood at NextHealth Los Angeles for a Micronutrient Test. Finding critically low micronutrients in his blood was a key part of informing Nick’s personalised longevity supplement regime.
You mentioned screening and labs … could you talk about how someone would put together that screening profile for themselves?
NE at 10:10
That’s part of my obsession - trying to figure this out. There's simply so many tools at our disposal that we need to start with that simplifying lens that brings the scope down.
I've played around with many different technologies, some of which are a few thousands of dollars, some of which are less than 100 bucks. I’m continually working to pull together examples of how to use these different tests, or different blood screens or biological age estimates to really formulate a way of creating self experiments that show what works for you.
But even that's a bit advanced. So how do we really bring this back to the basics? Moving beyond that family health questionnaire, the place that I'm increasingly looking to is genetics.
How Do Genetics Influence Longevity?
There's been a big spike in recent developments and the capability of analysing the genome… what's happening is that computational resources and machine learning and data science are coming together with genetic information that's being studied... coming together in a way where we can not just look at single parts of the genome, but look at hundreds of thousands to millions of parts of the genome and pull together a picture with that, using machine learning and data science approaches.
Self-Decode, a comprehensive genetic testing kit for less than $100USD. Use it to customise your longevity strategy by targeting your stack-building and lifestyle changes toward future age-related disease risk.
We just interviewed Joe Cohen (Founder at SelfDecode) on Longevity Blog… 60+ scientists and data machine learning data science folks who are really moving the needle on the capability of genetic analysis.
What they've been able to do with the advances in the science is personalise analysis and suggestions … now we can look at an individual and say… here are the specific diseases we can connect your risk to, for cardiovascular disease, or for neurodegenerative disease, or for metabolic disease. And these are the age related diseases.
Again, use it as a simplifying lens in the overwhelming space of all the things we can do… to work toward avoiding age related disease. And to start doing that 10 to 20 years ahead of time… you can start being proactive in changing your lifestyle in a specific way
Epigenetic Testing for Longevity (including Biological age)
RL at 15:04
Are you aware of any other companies that are looking at the epigenome for doing machine learning of the same thing with, you know, methylation clocks?
NE at 15:49
Yes. This is where things are going now. Epigenetic understanding in science has really accelerated over the last five years, again, because of the ability to sequence and be able to do that types of real in depth analysis to pull the data out of the epigenome which is changing over time, which is responding to the environment.
...That space is a bit behind, you could say it's 10 years behind genome sequencing, and that we're still connecting what's happening in the genome to outcomes.
I've spoken with the CSO of Chronomics Dani Martin-Herranz, which is one of the leading companies in epigenetic analysis … we get a biological age number, but how do we know.. what we should do to improve that biological age?
Order your own epigenetic biological age test from DoNotAge. This kit includes customised insights into gut, vision and cardiac health. Use the code “longevityblog” to save 10%
The fact is that the data is not there yet, the science isn't there yet to say this is what the epigenome is showing us.
This is what you need to change to be more youthful or to solve a given problem…it's a even thornier problem than simple genetic analysis, but it will increasingly inform us on our health journey, particularly our longevity journey, as it's becoming central to understanding some of the ageing process itself.
what can biological age tell us about longevity?
RL at 18:36
Dr. Morgan Levine and some of the others from Yale and other places - they're finding that depending on what you train it on, the clock is going to be biassed towards cardiovascular risk or dementia risk or other risks like that.
NE at 20:15
I can add a few things there - Dr. Levine… I've watched several of her lectures, they've done some great collaboration with National University of Singapore talking about biological age clocks… what's happening biological age clocks is trying to express risks in the mortality space over time [to] represent your risk for a disease outcome.
That [biological age] number at the end is nice for a consumer because it's an easy story. But what's more interesting to me and where I think we're going to future is increasing dissection of those results to give useful information.
[Checkout 3x FREE ways to estimate your biological age!]
You mentioned Gordan Lauc from GlycanAge - we’ve interviewed him on Longevity Blog .. I actually just successfully improved my GlycanAge, it was our I'm 35, it was 30, I got it to be 24. I did this by eating a diversity of plants in my diet...
Nick improved his biological age by 6 years through a change in diet. How? By eating 30+ different plants per week. Checkout the details here!
Being able to use these tools to improve a biological age result does seem to suggest an improved health outcome.
But what's really interesting about the GlycanAge product is they actually break it down into three indices… you can actually look at these indices and see where you improved by trying an intervention.
… When you start to break down that result beyond just an age, you start to see, okay, I've increased my performance by reducing the number of inflammatory glycans in my body, which are causing chronic inflammation, and increasing the number of good glycans in my body, what you're saying to the rest of the body is systemically toned down inflammation… that's better for your longevity.
Reversing Aging versus Improving Biological Age
RL at 24:07
The question is if we reverse DNA methylation, have we reversed our risk of ageing?
NE at 24:47
This is important to get this out there for the consumer. There's a lot of different biological age tests. They will give you a result that comes out of a model that is trained that has some value.
If you get a number that says you're 40 years old, and you're 50, you're biologically younger on that metric, which is probably better than your peer who is 50, but gets a biological age of 60. There's some merit to the absolute value here.
But what's more interesting to me, and I've talked to Professor Lauc at GlycanAge about this, is that changing our biological age, the relative value… [getting a] lower value is indicative of making a positive health change wherever that model is trained.
Want to go deep on biological age models? Checkout our technical interview with Deep Longevity CLO Alex Zhavoronkov.
For glycans, the overall inflammation in your body. We're not talking about a single marker like C reactive protein, homocysteine… we're talking about 24 different glycans that track and tag the individual molecules in the body to tell the immune system what to do, before any of those blood markers go up.
The consumer needs to know what they’re trying to change based on which biological age test they’re using and what it represents. Then the should try to implement a positive change to that number, and testing again, some months later.
They also need to know how long that marker takes to change. With GlycanAge, you can change in just three months. With an epigenetic age test, it might take 6 to 12 months. So understanding the science and tech behind the biological age tool that you're going to use is part of what we demonstrate on Longevity Blog.
… One other thing I'll add - don't get caught up in calling it “reversing” ageing … No, you have improved your mortality risk because that age has gone lower. That's a great thing. But we're not at a point where we can “reverse” true biological age, in terms of turning that number down with interventions.
… The point is we have a couple new metrics that we can use to run self experiments and improve the longevity outcomes for our body, which is fantastic.
Biological Age in Athletes: Exercise and Longevity
RL at 28:31
One promising longevity molecule Urolithin A is making a big impact in the athelete work. Supplement “Mitopure” is demonstrating improvement in endurance performance through enhancing mitophagy (the death of defective mitochondria). Read more in our interview with Amazentis CMO Federico Luna.
That's a great point... I wanted to get what's your take on biological clocks measured in extreme athletes, they've noticed shortening of their age (increased biological age). Have you encountered that at all?
NE at 29:12
Yes. In fact, GlycanAge is a great example of this.... I am convinced far and away the best, the most powerful longevity drug you can take right now is exercise.
Now, exercise is an interesting drug, in that its doses are widely varying, and they're highly personalised. I recently did a deep dive on exercise and its profound benefits for longevity, and I decided that I wanted to really up my fitness game, and I actually became a triathlete.
So now I'm training for triathlons. And it's been a huge change for my body. I've seen so many positive things that have resulted from that. But I know that ... there's a so called J shaped curve, which is well known in the sports medicine industry. Once you exercise too much, you start increasing your risk, particularly for health conditions like atrial fibrillation
...There's risks that athletes face because when it comes down to a real true athlete, these individuals are pushing their body so hard day after day after day… exercise produces a profound amount of damage and inflammation in the body that the body that needs to recover to become stronger.
Over time, continuing to push your body really, really hard, like a professional athlete does, isn't actually probably good for longevity… I don't know where the bottom of that curve is, but it somewhere around 450 intensity minutes of exercise a week, according to big cohort studies.
So there's, you can do a lot of exercise. And you should, because it's a really good drug and it keeps improving your health outcomes. But professional athletes are on the far end of that. And this is why we see, you know, decreased benefit to high levels of really intense exercise, it's just simply too hard on the body for it to recover all the way.
RL at 33:19
Well, now that we're talking about some lifestyle things like exercising.. What about diet? Fasting, we hear so much stuff about that and longevity. What's your take on fasting influencing longevity?
Longevity Strategies for Fasting, Diet, Sleep and Stress - Read More in Part 2!
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It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
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I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Increasing Plant Diversity Improves GlycanAge Significantly - A Self-Experiment
First things first - we have a 15% discount code available for the GlycanAge test - ‘LONGEVITYBLOG’.
Now go run your own self-experiment!
Glycan Age Test Self-experiment Results
In a series of recent posts, Longevity Blog has been investigating glycans and their many important roles in the body.
There is much to learn, but the key takeaway is that they play an informative role to the immune system by ‘tagging’ which of the many foreign molecules in the both are friend and which are foe.
We’ve some ideas on how you might improve your GlycanAge - by eating more types of plants! Read on for more!
If you’re across the basics of how the immune system works, you’ll be aware that inflammation is a sign that the immune systems is activated.
And while this can be highly valuable for enacting repair of specific areas of the body (e.g. damaged tissue), it is also a destructive process (e.g. tear down and rebuild that tissue).
As we age, levels of chronic inflammation rise, both as a result of and a cause of the aging process.
In your quest to maintain your ‘youthfulness’ and achieve longevity, monitoring and improving levels of inflammation in your body is highly important!
However this has not always been easy. There are many ways to measure inflammation in the body - which to choose? How to improve it?
It turns out, there is a simpler answer - don’t track the result of inflammation, instead track the molecules which signal - should inflammation be ‘on’ or ‘off’?
That line of thinking brings us to glycans and specifically the GlycanAge biological age testing kit.
In this post, we’ll review the results from our Founder Nick’s GlycanAge self-experiment. For the nitty-gritty details on the how & why the experiment was conducted, including the hypothesis and scientific framework, be sure to read that post first!
Read on for a few basics, and then a deep dive into the results.
Self-experimenting with diet to inform the immune system
Hey everyone, Nick here! I’m excited to share with you that I was able to improve my GlycanAge by 6 years in just 3 months, with a specific dietary change.
That change? Eating at least 30 different plants per week.
This self-experiment was completed in effort to improve a GlycanAge that was already quite favourable (30 yrs for a 35 yr old) in an individual who was already ‘doing all of the right things’ with diet, exercise, sleep and stress.
From my perspective, -5 years just wasn’t quite good enough. I was convinced I could improve further, as I’d achieved much younger biological age by other measures, and I like a good challenge!
To complete this self-experiment I dutifully designed and tested a specific hypothesis, which was:
“By programming the immune system with a diversity of plant information (local & organic where possible), chronic inflammation will be reduced as the immune system learns more about what is friend and what is foe, leading to an improvement in the Glycan Age”
Let’s briefly talk about why adding more plants to the diet could be reasonably expected to improve GlycanAge and then take a look at the evidence which shows it worked.
Why would 30 plants per week improve glycanAge? The basics
Of course I suggest you read the introductory post, which will offer you much more detail, but here is the main line of reasoning why eating a diversity of plants is likely to improve your GlycanAge.
Delicious veggies from our local farmers market. Full of environmental information just waiting to program your immune system. Eat me!
The immune system is constantly monitoring what you eat - deciding what should and should not be allowed into the bloodstream.
This surveillance occurs in the small intestine at your “intestinal epithelial cells” (IECs) which act as a filter, whereby nutrients, electrolytes, water and beneficial bacteria are allowed into the bloodstream (while the ‘baddies’ are not)
The immune system that is supporting the IECs with this ‘filtering' step is learning what is good and what is bad through the diet you eat
This effectively means that your diet is information about your environment
The diet is then responsible for telling the body, through a diversity of food and organisms, what is ‘friend’ and what is ‘foe’ - and it does this through partnership with glycans
Thus the hypothesis:
When you don’t eat a diverse diet your immune system receives less information = more inflammation (and higher GlycanAge)
However, the opposite is also hypothesised to be true: more information = less inflammation (and lower GlycanAge)
Did it work? Experimental results
The results from this self experiment are provided through the GlycanAge online dashboard, which delivers a biological age result, but more importantly, a breakdown of the three most important glycan indices.
These indices summarise the 24 glycan types which regulate inflammation in the body, and are broken down in GlycanAge test results as follows:
G0 are glycans without galactose, which are the most proinflammatory. These are represented by the Mature Index.
G2 are glycans with two galactoses, which are suppressing inflammation. These are represented by the Health Index.
GS are glycans with sialic acid, which also suppress inflammation. These are represented by the Youth Index.
Result: GlycanAge improves by 6 years
I am presently 35 years old. My GlycanAge at the start of the self-experiment was 30, an encouraging result. After eating 30+ plants per week for 3 months, my GlycanAge further improved by 6 years, to a value of 24.
If you’re interested to understand a bit more about how this biological age estimate works, you can read our interview with glycan expert Prof. Gordan Lauc.
One very important question that we asked Prof. Lauc was about the importance of the absolute value of biological age versus the relative changes that occur over time.
“It’s also important to not worry about the absolute number, because the absolute number is also strongly affected by genetics. Approximately 30-50% of the GlycanAge is determined by your genes, you cannot fix it.
It is the relative number, the pace of changes in biological age which are important. If your GlycanAge is increasing more slowly than your chronological age, then that’s good. ”
My GlycanAge at the start of the self-experiment.
My GlycanAge at the end of the 3 month experiment.
Result: glycan indices improve across the board
One aspect of the GlycanAge test kit that I really like is that they give me direct access to raw data, a summary PDF report and insightful indices which breakdown the biological age estimate further.
Not many biological age test kits will offer you this level of detail, and it provides an important layer of additional insight into why a given self-experiment worked/didn’t work for improving biological age.
Intriguingly, the self-experiment resulted in across the board improvements in these indices. The changes in the % relative to my peers (percentiles) reveal this in a straightforward way.
For example, the ‘Health - G2’ index improved by 0.11. What does that mean? My result is now better than 60% of others in my age group, whereas before it was only 49% (a below average result).
The three major glycan indices at the start of the self-experiment.
The three major glycan indices at the end of the self-experiment.
Improving GlycanAge with diet: Discussion
Interpreting the results of a self-experiment is very important. We cannot simply look at the data in results form and make a conclusion. In the spirit of science, we must discuss them!
The most important aspect to discuss here, is how the self-experiment was controlled. In essence, this means limiting as much as possible, any external factors which could ‘confuse’ the results.
Importantly, we need to examine any changes in the four main drivers of GlycanAge results. As Professor Lauc outlined for us in his in-depth Longevity Blog interview, these are: stress, sleep, exercise and diet.
Let’s briefly review each.
Controlling Diet
I kept a simple list organising plants I ate into groups of 10 for each week of the self-experiment. This was done in the ‘notes’ app on my iPhone and was very easy to manage.
In our experiment we turned the ‘diet knob’ in a very specific way. By introducing the primary experimental change of eating 30+ plants per week.
First of all - compliance. I can confidently report that I was fully compliant over the 12 week period of experimentation.
In no week did I eat less than 30 different plants. I ate as many as 40 different plants and as few as 31 different plants.
I did not change my dietary protein, carbohydrate or fat ratios or overall intake of calories.
Inevitably, I did eat more soluble fibre due to increased plant diversity, however, I was already eating many organic vegetables and select fruits to begin with.
I just was not eating many different types, instead favouring about 10-15 different plants which I ate repeatedly.
It was as a fun challenge to find new plant foods to try! It resulted in my whole family eating more plants as well - an added bonus.
Controlling Sleep
As any good longevity focussed biohacker, I’m quite religious with my sleep schedule.
During the experiment, I did not change my bedtime or my wake-up time. There was no significant changes in sleep duration or quality. I also did not change any sleep-related supplements.
As monitored by Oura Ring, sleep time was between 7.5 - 8 hours per day with a sleep score of 80 on average.
The below is a gallery of images you can click through (4 in total) showing the sleep score and total sleep from early and late in the self-experiment.
Controlling Exercise
As set out in the opening post for this self-experiment, I maintained a consistent exercise load to within 10% on average (in a given month) as measured by my Garmin smartwatch and heart-rate monitor.
No significant changes were made to total time exercising, exercise intensity or the type of exercise I was completing.
I kept up my routine of 4 weeks of triathlon training with a one week de-load. Average load over the period was unchanged at around ~750-800.
Controlling Stress
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This aspect of the self-experiment was more interesting! I’d originally set out to complete this experiment over 6 months with two GlycanAge tests. However I cut it off at 3 months. Why?
Australia went into a sudden COVID lockdown, upending my life routine and introducing significant additional stress (homeschooling in and of itself would confound the results, haha!).
I simply could not continue the self-experiment for the additional 3 months and maintain good control over the experiment.
Thankfully, I was able to complete the 3 month self-experiment with no significant lifestyle or stress related changes. So this was well-controlled overall.
Conclusion: Eating a diversity of plants significantly improved my GlycanAge
To design this self-experiment, I used Dr Jenna Macciochi’s suggestion to eat 30+ plants per week to boost the immune system.
Immunity: The Science of Staying Well is one of the most up to date, accessible and helpful books out there on building a healthy immune system. Check it out! (Amazon Affiliate link)
We are fortunate to have a pretty clear cut result in this self-experiment.
It was well-controlled and occurred over a short-time frame, with very limited opportunity for external factors to confuse the result.
Moreover, the magnitude of the change in GlycanAge was significant. A 6 year improvement is well outside the measurement error.
Had my GlycanAge improved by only 1-2 years, we would not be able to make such a strong conclusion.
In addition to the size of the change in GlycanAge, there was significant improvement in all three of the glycan indices, where I improved by ~10% in age group relative terms.
This firmly suggests hypothesis looks to have been ‘proven’, with the expressly limited scope of this being an ‘n of one’’ dataset.
Conclusion: Eating more plants improves GlycanAge (for me, and maybe you as well!)
Practically, what does this mean?
For one, I know that I should most definitely keep eating 30+ plants/week! I now consider this part of my longevity strategy.
This is in addition to other tactics like supplementing with NMN, which I also determined to improve my biological age through a seperate self-experiment.
This is precisely how we should use these types of tests. In an intentional and controlled way to test a change and see if it helps you in your longevity journey.
While the ‘conclusion’ is only applicable to myself, this design of this self-experiment provides the opportunity for other wellness and longevity enthusiasts (that’s you!) to use this approach to improve their biological age.
However, if you do not already have healthy diet, exercise, sleep or stress habits - start with those first! Don’t forget that losing weight is the surest path to reducing inflammation and improving your GlycanAge (we asked Gordan!)
If you plan to give it a try, be sure to reach out on Twitter or Instagram and let me know!
You can check out GlycanAge test kits here, and don’t forget to use the code “LONGEVITYBLOG” to save 15% on your order!
Follow me on Twitter for the latest #Longevity news!
-
RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
-
My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
-
It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
-
“The #longevity segment opened my eyes to the groundbreaking advances in biotechnology, health, and wellness. The i… https://t.co/F8YB7PAeMW
-
I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
-
Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
-
RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
-
Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
I also posts related #Longevity content to Instagram as well, follow me @nickengerer
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Genetic Risk Analysis for Longevity: An Interview with Self-Decode Founder Joe Cohen
Do Genetics Determine Longevity?
The simple answer is ‘No’. Genetics do not determine longevity.
Longevity is a determined by a multitude of factors, including your environment, socio-economic status, risk appetite and of course diet, sleep & exercise.
However, they do very much influence longevity.
And when it comes to your personal longevity strategy - the simple answer of ‘No it’s not genetics that will determine your lifespan’ misses this key point.
Perhaps most importantly, noting that genetics do not determine longevity ignores a very important point. Namely that in planning ahead for a long and healthy future - you as an individual are not a statistic.
So, How Much Do Genetics Affect Longevity?
Genetics could have a lot to say about your longevity as an individual in many cases.
We can point to several illustrations.
Do you carry the APOE4 gene that significantly increases risk for Alzheimers? What about the BRCA genetic variants that influence breast cancer (as well prostate cancer)?
What about Lp(a)? Do you carry the genes which lead to elevated levels of this nasty little lipoprotein? If so, your risk of heart attack at a young age is significantly elevated.
To answer the question, ‘do genetics affect (influence) longevity?’ - you need to look past the mainstream articles written to appeal to a wide audience.
They are borne from high level statistical analysis.
Does it it really matter to you what the genetics of countless others determine on average?
Of course not. As an individual it matters what YOUR genes say. And if you carry any of the genes we just mentioned, you’re at elevated risk of early onset age-related diseases.
That means genes could very much influence your longevity in a significant way.
What to do about it? Read on.
What Genetic Factors Determine Longevity?
Once again, searching the internet for this answer will bring you to a bulleted list of ‘major’ genetic factors that may influence healthspan and lifespan.
Big deal! Eye roll.
Why? Because these articles once again miss the point - you need to zoom in on your individual genetic risk profile to know what risk factors you carry.
Thankfully, on this personalised assessment front, there is welcome news.
Progress in genetic testing and genetic analytics has moved incredibly quickly over the past decade.
Perhaps most importantly these advancements have been in both cost (genetic sequencing is getting cheaper) and importantly the algorithms that can connect scientific studies about specific genetic variants to disease risk.
And not just any old risk - your risk.
These technological advancements are now able to get quite specific about that.
Let’s talk about ‘the how’.
How reliable is genetic testing in predicting disease risk?
If you haven’t been paying close attention to this space, your knowledge on the topic is likely quite dated.
The answer this this question, just a few years ago was bleak - simply put, genetic testing was not very good predicting disease risk.
However, the rate of innovation with genetic analysis has been particularly quick over the past few years, and through technologies like artificial intelligence, it’s picking up the pace.
Self-Decode’s DNA test kit is mind-bogglingly cheap, at only $90. We’ll learn how they use an advanced machine learning process call ‘imputation’ to analyse your genome in a very targeted way, to keep costs down, while delivering a very deep analysis.
If we want to understand how reliable genetic testing can be for assessing disease risk (and thereby your longevity) we need to get past the dated & mainstream and up to the front of the pack.
Onward, to the forefront of genetic analytics!
This takes us to the exceptionally impressive data science, genetics and science team at Self-Decode.
They have recently developed some remarkable capabilities for genetic testing (low cost & accurate) and analytics (years ahead of the competition).
Most importantly, they’ve also built a successful platform for delivering personalised insights about your longevity risks AND what you can do about your risks.
How have they done it? We’re glad you asked…
Next Generation Genetic Analytics: An Interview with Self-Decode Founder Joe Cohen
In order to better understand Self-Decode’s mission and the capabilities of their team, we interviewed their Founder and CEO Joe Cohen.
Joe Cohen is the Founder and CEO at Self-Decode. He is an avid biohacker and self-experimenter, as well as a respected entrepreneur.
You may be aware of Joe’s earlier work on the website ‘Self-Hacked’, which is one of the most widely used and thoroughly cited biohacking websites on the internet.
When we interviewed Joe, asking specifically questions about longevity and genetics, we were very impressed with the capabilities they’d developed.
Perhaps most interesting was Joe’s announcement of the arrival of a ‘2nd generation’ of genetic analytics.
This 2nd generation is powered by artificial intelligence and advanced data science, which has recently become capable of providing a level of insight health enthusiasts, biohackers and longevity junkies (like you) have been left wanting to date.
Namely - what should I be doing to manage my personalised risk?
Personalised Genetics Insights with Actionable Information? Finally!
As we said at the opening - simply put, early stage genetic analytics have been fairly disappointing.
Direct to consumer genetic analytics really hasn’t really proven all that useful for the everyday wellness warrior and longevity enthusiast.
However, at Longevity Blog, we believe we are entering a new era of test at home genetic kits.
We’ll help highlight why this is the case through our discussion with Joe and in upcoming posts which dive into Self-Decode’s online genetics reporting and analysis platform.
When we’re through, we expect you’ll feel confident that Self-Decode genetic reports can become part of your personalised longevity strategy.
We’ll also take a look at their LabTestAnalyzer platform, including insights from a self-experiment run by our Founder Nick to radically reduce his LDL-C cholesterol levels.
Let’s get onto that interview!
This interview was conducted over Zoom during August 2021. It has been edited for brevity, conciseness and correctness.
Longevity Blog (LB): Joe, to kick things off, tell us about SelfDecode, its mission and purpose as a company, and what is your team's united behind? What's your mission?
Joe Cohen (JC): Our mission is to improve people's health. That's really what it comes down to in a very small nutshell. The real question is: what is the best way to do that? We think it is through personalized health strategies, looking at DNA and lab tests, and giving more precise recommendations.
One defining aspect of Self-Decode is the incredible scientific & data engineering team they’ve built. With 85 people in the company nearly 70 are dedicated to making their genetic testing & analytics better every day! Meet the team here.
LB: A core part of the offering from SelfDecode is genetic testing. In several recent interviews, you've been discussing the arrival of ‘a second generation of genetic analytics’.
In these interviews you specifically discussed the involvement of artificial intelligence. Introduce us this ‘second generation’ concept - in particular, how SelfDecode’s offering differs from other apparently similar services.
JC: Most companies that are doing genomics are not actually doing personalised health. Actually, none of them are, really. In order to do the analysis right, it takes a lot of very specialized skills that are hard to come by.
Very few companies are actually doing this and no B2C (direct to consumer) companies are doing genetic analysis correctly. 23andMe may be one company that's doing the analysis correctly, but they're not giving precision health recommendations.
In order to do genetic analysis correctly, you need to look at millions of variants. Whereas most companies are only looking at a handful of variants, and then making conclusions based on that.
Number one is they're not doing the analysis correctly. Number two is not giving precision health recommendations.
In order to do these both well, you do need to use AI and deal with large amounts of data. That's a big computational challenge and a major reason why companies are not doing this.
Single Nucleotide Polymorphisms
“In order to do genetic analysis correctly, you need to look at millions of variants.”
LB: One of these challenges and points of contrast is the analysis of single nucleotide polymorphisms, or SNPs, and the limitations of looking at individual SNPs.
Second generation analytics is looking at much more than a single SNP - it is instead looking at many, many points in the genome. Can you explain how that's important for creating that personalised guidance you're describing?
JC: First, looking at many points is more important for genetic risk for a disease. If you're only looking at one SNP - it's like looking at one letter in a book, right? Not even one word, just one letter.
Single Nucleotide Polymorphisms refer to a single location in the genome which may vary from individual to individual. Most genetics analysis test kits look at single SNPs to provide limited insight.
Self-Decode is different. They look at many thousands to millions of SNPs to provide you with personalised guidance.
Sometimes if you look at a few key variants, you might be able to spell a whole word, and that may give you some insights. But more or less, looking at a few letters and coming up with broad conclusions means you’re missing tons of information.
The future of genetics is with AI. But using AI means you need to build an entire data analysis pipeline to look at the holistic picture for risk.
Then after that, if you want to provide personalized information, you can use labs and environmental risks to get a more of a whole picture. That's what Self-Decode does.
Combining Genetic Analytics with Blood Tests
LB: In terms of that actionable, personalised guidance, you have just mentioned analyzing labs in conjunction with genetic risk factors. Your platform then goes on to recommend supplements and lifestyle changes based on those results. Could you provide an overview on how that works?
JC: Users can upload lab results that they get from a doctor using our LabTestAnalyzer and then receive information about the optimal ranges for each blood marker. We then provide recommendations on how to get these markers into the normal or the optimal ranges.
We're working on combining the labs, the environment and genetics in order to create a more holistic picture about what is going on in the individual. And then provide them with the best recommendations to get them into being optimally healthy.
Self-Decode’s Deep Scientific Expertise
“We have a team of 85 people with about 65 to 70 in the science, engineering and development space”
LB: One of the things that SelfDecode has accomplished which is quite unique in this space is assembling a very capable and diverse team of scientists, engineers and software developers to do this type of work. Can you tell us a little bit about your team? What does this team look like? What are they doing?
JC: We have a team of 85 people with about 65 to 70 in the science, engineering and development space. We need a large data engineering team, because we are dealing with lots of data. We also have bioinformatics scientists and genomic scientists, as well as software developers who have to become familiar with these topics.
Our team of software developers, over a couple years, have become more like ‘genomics developers’ really. Many of the data scientists are experts in machine learning and AI.
LB: That team sounds quite diverse and capable. This depth and diversity is one of the reasons Self-Decode has come out with such a high quality product.
Innovating on Genetic Testing Kit Price
Self-Decodes’s genetic test kit is far and way the best value for this market category.
Through the process of ‘imputation’ to scale up your genetic sample, they can offer a low price kit ($100USD) with the equivalent deep dive genetic analysis of kits which are many times more expensive ($500-$1000USD).
LB: One thing we’d like to ask you about is the cost. The price point for entry is pretty attractive, at around only $100.
Using your genetic testing kit, you’re able to directly test on the order of 700 - 800,000 points in the genome. But then you use some fancy AI techniques to scale this up to 83 million locations.
This process of ‘imputation’ is used to fill out the genomic data with a high level of accuracy. Explain this process to our readers.
JC: We have an imputations team that are working on creating more accurate predictions of SNPs not directly sampled.
We use AI to predict based on the patterns that we see. There are actually pretty good prediction methods for this that enable us to predict 83 million SNPs from the 700,000, which is basically all the snips that you have with 99.7% accuracy.
LB: Using this imputation process, you’re able to produce some impressive level of detailed recommendations.
That team, the algorithms and the product have enabled SelfDecode to move beyond a simple genetic risk score style approach (typical for the genetic testing industry) and onto specifically guiding users on what disease risks will be present for them in the future and how they can minimise those risks.
Genetic Reports with Personalised Guidance
Self-Decode’s Cardiovascular Disease Report can reveal much about your risk factors for developing cardiovascular disease.
LB: You present this information to the user in a series of customised reports, each dedicated to a specific category. Could you walk us through some specific aspects of your reports?
In particular, our audience is very interested in longevity. You have reports on cardiovascular disease and cancer, as well as diabetes and metabolic disease. Tell us more.
JC: We have a bunch of different topics. And you know, topics like cardiovascular disease are very important for longevity. Blood sugar is very important for longevity. Every report looks at a different number of variants - usually around 1 million.
Then we also have to look at your ancestry as well, that's something that we're working on. We have an entire team that's working on ancestry, because your ethnicity plays a very big role in your risk.
For example, if a study is done on a Japanese population, it may not have applicability to you (if you’re not of Asian descent). A study done on a different ethnicity doesn't have a good chance of being applicable to you.
The report then gives a prioritized list of recommendations that change based on your genetics. So we do a very deep dive into the interactions between genes and specific health recommendations. We also give the supporting evidence behind those recommendations - everything's referenced.
LB: Take for example your cardiovascular disease risk report, it reviews different types of cardiovascular disease risk from strokes to vascular complications to congestive heart failure.
The report, using the genetic information we just discussed, then provides specific personalised guidance for the use. One thing we love about these recommendations is that they go beyond the typical “exercise and eat well” guidance and get much more specific.
For example, the cardiovascular report for our Founder Nick recommended quercetin and calcium supplementation.
Personalised recommendation delivered to our Founder Nick after he ran his cardiovascular disease report on Self-Decode.
Self-Decode Delivers Priority Ranked Personalised Recommendations
LB: What can users expect when they complete the genomic testing kit and access their reports. We assume that the recommendations are different for everyone?
Self-Decode have a dedicated longevity report which details personalised risks in the aging process. You can review it here.
JC: Yes. These are priority listed, meaning the top recommendations go up and down the list based on an individual's genetics.
LB: Right - that's the real winner there, a key differentiator. It is personalised guidance, we like that!
One of the reports is actually dedicated to longevity specifically. It reports a personalized risk profile for oxidative stress, inflammation, cardiovascular disease, and DNA repair.
For users interested in assessing risks to their longevity and optimising their healthspan, how can the Self-Decode platform help them optimise? What do you think, Joe?
JC: I would certainly look at the recommendations in the longevity report and then implement those recommendations. They're a bit different with everyone.
Joe’s Personal Longevity Strategy
LB: In terms of thinking further about this topic of risk and longevity and using Self-Decode, let’s talk a bit more about your own health optimisation journey.
Your original work was on the website Self-Hacked, before going on to found SelfDecode, and was largely inspired by your own personal biohacking journey. Share with us how the Self-Decode platform helps you make decisions on your own personal longevity and wellness optimization?
JC: The platform is quite useful to explore the many different topics I am interested in. I'll look at the report recommendations, and then I'll look at which genes are involved. Then I go ahead and try out the recommendations. Every report can be used to add new things to your personal health regimen.
I also look at my labs (on Lab Test Analyzer). For example, if I have high blood sugar genetic risks, I look at my labs and track that. The same can be done with high cardiovascular risk, where I look at triglycerides, HDL and LDL.
“The more you are learning about aging, your health - you’re just going to be more healthy”
Some things are for longevity, and then there's things for more the short term. For example, the mood report. That's a big thing I'm looking at. What are the things that I could do to improve my mood? I’ll take the report recommendations and start implementing them.
It gives me more motivation to continue with my personal journey.
LB: Could you share a specific example? Perhaps a specific example of something that you were recommended where you tried it and it helped?
Joe’s Self-Decode Mood Report steered him toward 5-HTP. A great example of how personalised guidance can improved overall wellness more effectively than flying blind.
JC: Definitely. 5-HTP was a big thing for mood, because of the various serotonin genes. And that came up on my reports, and I implemented that, it had a positive impact and so I have been taking it ever since.
LB: This type of wellness feedback loop is one of the things we think your platform is most powerful for.
As we wrap up the interview, let’s talk a bit more about you. We ask all of our interviewees to share part of their own personal longevity strategy.
What is your strategy for maintaining your health in your 60s, 70s and beyond?
To Be Healthier, Make Learning about Health Your Hobby
JC: For me, it is very much about the motivation to be healthy. It’s like exercise. Everybody knows they should exercise, but not everybody does it as much as they need. I think you need to find motivation to do it.
This is where health education comes in. For example, like reading about your health - the more you are learning about aging, your health - you're just going to be more healthy. If you're reading health articles, reading your genetic reports, tracking your results - you're just going to be more healthy, because you're into it.
The other big thing is knowing what to do. Many people are lost, and they don't know where to start. What's the best thing for them? It's important to approach where that starting point is. Disease screening and the report recommendations give you something specific to try out and see which one works the best for you.
There's still some of that self experimentation. But our reports give you the things that you should be trying first.
LB: That's a great answer, Joe. We love that you hit on those longevity topics.
Thank you so much for your time today, Joe, we really appreciate you coming to tell us about SelfDecode. We think it's a fantastic platform for health optimization, and your answer about making health a hobby - SelfDecode enables that directly.
Thanks again Joe!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Self-experimenting with GlycanAge - Before and After Diet Changes
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Simply use the code “LONGEVITYBLOG” at checkout
Glycan Age Test review & Self-experiment
As we’ve learnt over the past few posts, glycans are incredible molecules with many important roles in the body.
Perhaps the most important of which is providing information to our immune system about what foreign molecules (i.e. diet, dust particles, bacteria, etc!) are friend and which are foe.
My GlycanAge biological age test kit - just a few drops of blood, drop it in the envelope & it’s ready to go!
As such, they strongly regulate inflammation in to the body, and as we’ve learnt - they are impressively capable of predicting age-related disease onset.
Also, their ‘youthfulness’ can maintained by paying attention to certain lifestyle factors - chiefly diet, exercise, stress and sleep - monitoring them can help us track how we’re doing as we biohack our way to long & healthy lives.
In this post we’ll cover:
The role of glycans in immunity
How glycans are involved in the digestive system
How to use diet to improve GlycanAge
Why food is information for the immune system
Setting up a self-experiment for improving GlycanAge
Plus - snippets from our interview with world expert on glycans - Professor Gordan Lauc
Glycans Regulate Immunity
It is the role of glycans in immunity and disease related processes which makes them so important with respect to the aging process.
Such is their potential impact, that any personalised longevity strategy should likely include an effort to maintain youthful glycan characteristics.
A tumour cell being tagged with 'bad guy’ glycans (represented by the squares, circles, diamonds on cell membrane). Image credit: Gly-tech
“Youthful” in this context essentially means ‘anti-inflammatory’, meaning:
the immune system is not overactive
chronic inflammation is not present (or in advanced age, well managed)
the ravages of inflammaging (the negative feedback cycle of inflammation creating more damage & inflammation) are avoided
How Glycans Impact the Immune System
As we learned in our exclusive interview with world expert in all things glycans, Professor Gordan Lauc, glycans keep track of foreign materials in the body, tagging them as ‘friend’ or ‘enemy’ so that our antibodies know whether to activate inflammation (attack) or suppress inflammation (don’t attack).
“When antibodies are developed, they do not know whether a given foreign object will be an enemy, like a bacteria or a virus, or if it is friendly, such as food or a dust or something else they should ignore.
After the antibody binds to this foreign object, what happens next is determined by glycans. This very complicated process (glycosylation) is regulated by least 40 different genes.
These glycans decide whether antibody will kill a target cell (activate inflammation) or will it suppress inflammation”
Glycans, Immunity and Digestion
A major role of this immune surveillance process is centred on digestion. This is because the process of taking what we eat, and turning it into our own cells or energy requires active decision making on what should be allowed into the bloodstream.
Ultimately, food is “a foreign object” (using Prof. Lauc’s words above) that has entered the body.
This is clearly done for the purposes of providing fuel and supplying important nutrients, such as vitamins and minerals. However, much more than simple nutrition comes along for the ride.
This includes a host of ‘commensal’ (friendly) bacteria, and sometimes, bad ones, along with the occasional plant compounds that may stress the body (such as glycoalkaloids in the ‘nightshade’ family of veggies).
Our immune system has an important role to play in screening which of these compounds should be permitted to pass through the wall of the small intestine and into the blood stream.
We’ll revisit this in detail later in the post!
Using Diet to Self-Experiment with GlycanAge
I (Nick here! Founder at Longevity Blog) am currently experimenting with improving my GlycanAge through a change in my diet, and in this post, I’ll explain what changes I am making, why and how to make this self-experiment an effective one.
Changing diet to improve my GlycanAge - can it be done? Certainly - the question is - for relatively health people, how?
This self-experiment will explore a hypothesis related to increasing the diversity of plants in my diet and potential improvement in my GlycanAge.
However, before we get into the specifics on how this experiment will work, let’s introduce some important background knowledge to support the approach.
Improving GlycanAge with Diet
Improving GlycanAge through changes in your diet can be either quite easy or mysteriously challenging.
If you’re someone who needs to lose some weight - you’re in luck. You can very likely improve you GlycanAge by simply losing weight. Look no further than our interview with Professor Lauc for the reasons why:
“Longevity Blog: Could you point to a successful model for testing and improving your GlycanAge in a way that you can say, I know what did improved it, it was _____ ?
Gordan Lauc: One good example is weight loss. Losing extra weight helps the vast majority of people, because obesity is a big driver of inflammation.”
However, if you’re already at healthy weight, how to use your diet to improve GlycanAge is not immediately obvious. In fact, clinical research with GlycanAge and diet has shown this to be quite challenging (see below tweet & follow me on Twitter for more!).
1000 people were divided into groups eating very different diets
— Nick Engerer (@nickengerer) July 16, 2021
The outcome? It was impossible to predict which diet was best for whom
However, by monitoring glycans, that became possible. Their role in inflammation signalling can reveal - what diet works best for you? pic.twitter.com/D7AyNlzVfp
Improving GlycanAge with Diet by Eating More Plants
Despite this challenge, I believer I have developed a solid hypothesis for testing how people at a healthy weight may be able to reliably improve their GlycanAge.
Through some serious homework, I also believe that this proposed change in diet that would also have relevance to other self-experimenters, and it could be replicated reliably.
This approach will leverage the sub-process of our immune system screening food particles and non-human organisms (i.e. bacteria) as they are processed in the duodenum (small intestine).
This critical step occurs before entering food materials and/or friendly bacteria are permitted to enter the bloodstream and intimately involves - you guessed it, glycans!
Food as Information for the Immune System
To continue down this line of reasoning, you need to adapt your thinking of the small intestine. Stop thinking of it as ‘inside’ your body, and start thinking of it as ‘outside’.
It is within the small intestine where a critical decisions is made - namely, what foreign materials from the diet are permitted to enter the blood stream.
Pictured: Intestinal villae, lines with intestinal epithelial cells (IECs) along with several other functional cells include macrophages (immune surveillance cells). Image Credit: Nature Reviews: Immunology
The small intestine is lined with “intestinal epithelial cells” or IECs for short. IECs are a single layer of cells with two key functions:
1) be a barrier to anything harmful - toxins, bad bacteria, viruses or antigens
2) act as a filter, whereby nutrients, electrolytes, water and beneficial bacteria are allowed into the bloodstream.
In this secondary function of ‘filtering’ where a detailed and highly important involvement of the immune surveillance system takes place.
The details are vastly complicated, but we can afford a useful simplification here.
Assuming you have tight junctions between the epithelial cells of the small intestine, only the foreign material ‘accepted’ by your immune system is permitted to pass through.
Anything else - and your immune system signals ‘attack’ - producing inflammatory signals.
IGG glycolisation (that’s science talk for how glycans are being used within the body - read more about this in the interview with Prof. Gordan Lauc) plays a critical roles in this screening process, and the ‘tagging’ of foreign material as friend or foe is at its peak level of activity at this epithelial junction.
Critically - this highly complex process includes many trillions of bacteria, which participate in the breakdown and processing of food materials by the body.
These so called ‘commensal’ bacteria are actually actively recruited and ‘pulled through’ the epithelial junctions by the immune system.
The commensal bacteria are pivotal to your broader bodily health, with your overall wellbeing depending on a vibrant and diverse population of these friendly bacteria in the gut.
Food as Information
Local organic root vegetables from our weekly farmers market. Covered in healthy soil based commensal bacteria - just waiting to program your immune system.
The activities of food screening and bacterial populations in the gut are tremendously influential on inflammation in the body.
To better illustrate this, we’ll adopt a basic framework - where our diet is information about our environment.
This is the case because the food we eat, the bacterial populations in that food, as well as ‘antigens’ (‘bad things for us’) effectively ‘program’ our immune system.
In prehistoric times, this information was often life-saving, as it was critical for our bodies to become well adapted to the organisms, toxins and food sources around us in order to survive.
In this way, we evolved for our diet to signal “this is what your environment is like and thus how you should adapt to prepare for it”.
Now consider the modern environment, where food is sterilised and our environment is kept much cleaner than ‘nature’ could ever be. Your immune surveillance system is now cut-off from this critical source of information!
Why does this matter? Well, because in a relatively sterile environment, your body lacks enough exposure to healthy bacteria and the wide variety of food it needs to know when or when not to attack.
What does that mean? A sterile diet effectively means your immune system’s default mode is ‘attack’. The immune system, out of interest in self-preservation, will work to eliminate a foreign material it is not comfortable with (used to seeing).
Add it all up and you get - you guessed, more inflammation.
Eating a Diversity of Plants Programs Immunity
In viewing food and organisms from the environment as information, we can begin to build up our glycan self-experiment in the following way.
If your body is not provided a diverse amount of information about the environment through a diversity of food and organisms through the diet, it will tend to react with ‘attack’ more often.
Through our framework: less information = more inflammation.
On the flip side the pathway to reconciling the overactive immune system is through providing ample information about the environment through the diet.
Dr Jenna Macciochi’s Immunity: The Science of Staying Well is one of the most up to date, accessible and helpful books out there on building a healthy immune system. (Amazon Affiliate link)
This will then support the immune system with a more comprehensive view of what foreign materials are ‘friendly’ and which are not.
This conceptual framework is precisely what Dr Jenna Macciochi lays out in her book Immunity: Science of Staying Well.
One of the key recommendations from this exceptionally insightful book is to eat a diversity of plants regularly, preferably local and organic ones.
The result will be a stronger immune system, which Dr Macciochi argues, is one of the only *real* ways to “boost your immunity”.
In her book, immunity expert Dr Macciochi says there is a valuable ‘rule of thumb’ for improving your immune system with diet.
What’s the rule? We’re glad you asked..
“A good rule of thumb for the biggest impact on health is to aim for over 30 different plants per week.
Whereas the opposite is also true. Eating 10 or few has a potentially damaging effect on the microbiota”
Why is this the case? It’s all about diversity of information about the environment.
And that information is programmed in the body via your glycans.
GlycanAge Self-experiment: A Diet with Diversity of Plants
My GlycanAge as of April 2021 is already ‘favourable’. But that’s not good enough for a longevity focussed biohacker now is it?
How low can we go?!
Coming full circle, this logic leads naturally to the experimental hypothesis:
“By programming the immune system with a diversity of plant information (local & organic where possible), chronic inflammation will be reduced as the immune system learns more about what is friend and what is foe, leading to an improvement in the Glycan Age”
The is precisely the hypothesis that this self-experiment will evaluate. So let’s get down to it!
My GlycanAge was first measured in April 2021.
My GlycanAge is 30, whereas my chronological age is 35.
According to Prof. Gordan Lauc, this is a great result.
“Longevity Blog: What is a “good” GlycanAge result Gordan?
Gordan Lauc: Anything which is younger than your chronological age, I would say it’s good.
It’s also important to not worry about the absolute number, because the absolute number is also strongly affected by genetics.
Approximately 30-50% of the GlycanAge is determined by your genes, you cannot fix it.””
Self-experiment: Starting Conditions & Control
This result does make sense. In the 6 months leading up to this test, I maintained optimal levels of physical activity (training for sprint triathlons), a healthy balanced diet (eating small meals across the day, mostly vegetarian but with animal protein 3-5x/week), sleeping fairly well (Oura ring sleep scores at 75-85 on average) and well managed stress levels.
So in each of the four levy lifestyle factors (diet, exercise, sleep, stress) for my GlycanAge, things were in tip-top shape.
Do you think self-experiments are totally rad? So do we!
Subscribe to be notified when we announce the results from the GlycanAge before & after!
In this self-experiment, beginning from 1 May, I will eat 30+ plants per week.
Where possible, this will be from local and organic sources (of which we have plenty in the Byron Bay Area!).
Experimental Control
As discussed in my previous foray into self-experimentation with the NAD precursor NMN, it is challenging, but not impossible, to perform a well controlled self-experiment.
We approach this by keeping lifestyle factors as constant as we can, not changing any other key variables, and running the self-experiment for as short a time as possible.
For the GlycanAge self-experiment I will:
maintain a consistent exercise load to within 10% on average (as measured by my Garmin smartwatch and heart-rate monitor)
keep my same sleep schedule (7-8 hours a night)
not make any large lifestyle changes that might negatively impact my stress
not make any other changes to my diet (we’ll have to keep in mind that my diet will also have a reduction in non plant foods - to make room for all of the plants!)
Experimental Test Period
The experiment, according to advice from Prof Lauc will be run for a minimum of 3 months and maximum of 6 months.
This means I will re-test date on 1 August and again on 1 November.
I asked @GordanLauc - how often should we test @GlycanAge?
— Nick Engerer (@nickengerer) July 20, 2021
⁰⁰The half life of IGG glycolisation is ~3 weeks. 1 month would be the shortest period for re-testing
Lifestyle change effects take a bit longer. Modify diet, sleep, stress or exercise?
Recheck every 3 to 6 months pic.twitter.com/hjuVEdWIBo
Other Relevant Items
To keep track of my plant intake, and ensure that eat enough plants, I am keeping a weekly record of all of the plants that I eat.
I keep this pretty simple, recording them in the iOS notes app - presumably you could do this just about anyway that you please.
There is of course an important question - what is a ‘plant’? What counts as 1x plant?
I will only be counting whole food plant sources which equate to at least one serving of that food.
So for example, I would not count ‘bread’ to be a plant, although it comes from wheat flour at it is quite refined/processed (not a whole food). I would however count rolled oats as a 1x plant (limited processing, effectively a whole food item).
Follow our Founder Nick on Twitter for the latest #Longevity news!
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RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
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My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
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It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
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“The #longevity segment opened my eyes to the groundbreaking advances in biotechnology, health, and wellness. The i… https://t.co/F8YB7PAeMW
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I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
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Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
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RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
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Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
Nick also posts related #Longevity content to Instagram as well, follow him at @nickengerer
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN Transporter Slc12a8 and the future of NMN clinical trials with Dr Alessia Grozio
The need for NMN Clinical trials
In a recent post, we discussed a key barrier in our knowledge of NMN supplementation in humans - namely the very limited clinical trial data.
However, this barrier is soon to be removed, thanks to high profile research + business collaborations which a directly confronting this lack of information.
Dr Alessia Grozio is Chief Scientist at Elevant and a researcher at the Buck Institute, ‘insanely’ interested in all things NMN and longevity.
With their execution and success, we will soon have a clear understanding of the benefits of NMN supplementation in human subjects (well beyond simpler experimental results, such as how NMN improved our Founder Nick’s biological age by 3.5 years).
Collaborations on NMN Clinical Research
One such collaboration we recently highlighted was the the work between aging research leader the Buck Institute, Elevant, and its parent company Seneque.
Together they have developed a healthy pipeline of NMN clinical trials in humans, which will focus on muscle recovery after exercise, potential benefits to skin health and much more (details in our interview).
Today, we host Elevant’s Chief Scientist and Buck Institute Researcher Dr. Alessia Grozio (PhD) for an exclusive interview on the future clinical trial outlook for NMN.
Interview with NMN researcher and expert Dr Alessia Grozio
Longevity Blog contacted Dr. Grozio with a number of important questions on the topic of NMN supplementation in humans.
Seneque’s mission is to increase healthspan by 20% in the next decade.
One key topic area we addressed was Dr Grozio’s co-discovery of a transporter that delivers NMN directly into cells called slc12a8.
This discovery was the first time that a pathway for NMN to enter cells directly had been discovered. A key development which well renowned NMN expert Dr. David Sinclair was very quick to highlight in Nature Metabolism (read it here) .
This discovery has not been without controversy, as NAD biologist and researcher Dr. Charles Brenner was quick to criticise the study. This has led to a bit of a schism in the research community on whether or not slc12a8 does what Dr Grozio says it does.
So we wanted to hear it from the expert directly, asking Dr. Grozio to help us better understand the significance of slc12a8, particularly around how NMN enters the cell (which is critical for it to fulfil its NAD boosting function).
As always, we also ask her about her personal longevity strategy.
Without further delay - onwards!
This interview was conducted in written format over email correspondence during May 2021
Longevity Blog (LB): Dr Grozio, thanks for joining us here on Longevity Blog.
To kick us off - you work diligently at both a research organisation and a commercial venture. Surely its hard work! Tell us - what drives you? What brings you into work each day?
Alessia Grozio (AG): Thanks for inviting me. The passion for my work and an “insane” curiosity for anything related to aging/longevity and NAD+ biology that brings me to work every day.
After earning my PhD in biochemistry, I started working on the enzymes (sirtuins, NAMPT, CD38/CD73 ecto-enzymes) involved in NAD+ metabolism.
NAD biology is quite complex. This is an area Dr. Grozio finds quite fascinating. We do too!
In a previous post with Dr Grozio’s college, Dr. Eric Verdin, we discuss this topics in further detail.
I have always been fascinated by the pivotal role that NAD+ plays in maintaining homeostasis in our body and the plethora of cellular processes in which it is involved.
Therefore, investigating the effects of NMN (nicotinamide mononucleotide), a critical endogenous compound for NAD+ biosynthesis, in different physio-pathological conditions where NAD+ levels are impaired, was a natural prosecution of my scientific interests.
More than “hard”, I would say that my job, as for many other scientists, is never boring!
What is NMN-C
LB: Thank you for sharing those personal insights. One of the reasons we’re speaking with you today is to help introduce ‘Elevant’, and your efforts to make ‘NMN-C’ available to a broad audience.
Please introduce us to NMN-C. How does this formulation differ from other forms of NMN that our readership may already be taking?
“What makes our NMN-C special is the extremely high level of safety and development that has gone into it. ”
AG: What makes our NMN-C special is the extremely high level of safety and development that has gone into it. We think what is most important is providing consumers with NMN-based products that have the highest levels of safety and quality possible.
NMN-C is exclusively available through Elevant in their “Prime” product (pictured)
What’s critical is, once NMN has been synthetized, to characterize the impurities, filter them as much as possible to reduce them to the minimum, and make sure that the few impurities remaining are safe.
In our NMN-C the level of impurities is very low, complying with the pharmaceutical grade guidelines.
Our product is then tested at high dosage, pre-clinically and in human, to confirm it’s safe to use.
Is NMN Safe for Humans?
LB: There was a recent study specifically looking into the ‘safe’ level of NMN supplementation, could you share some information on this work?
“NMN-C at doses up to 1500 mg/kg/d appears to be safe”
AG: Our NMN-C acquired self-affirmed GRAS (Generally Recognized as Safe) status in accordance with US FDA regulatory guidelines, performed by an independent panel of toxicology and nutrition experts.
Moreover, we have recently published the first OECD 408 toxicology study performed on NMN. This study analyses the No Observable Adverse Effect Level (NOAEL) of our NMN-C and demonstrated that repeated oral administration of NMN-C at doses up to 1500 mg/kg/d appears to be safe and did not promote adverse effects in rats up to 90 days.
Diagram showing the role of Slc12a8 and how it enables NMN to enter the cell. Source: Nature Metabolism
Does NMN enter the cell intact?
LB: You made some waves in the research community with your published results on a NMN ‘transporter’ slc12a8.
This was a particularly exciting discovery, as the ‘doorway’ for NMN to enter the cell was previously unknown.
Could you briefly explain why this discovery is significant for the prospects of NMN supplementation?
AG: The identification of a novel NMN transporter, Slc12a8, further advances our knowledge regarding NAD+ metabolism by providing a new mechanistic insight through which the absorption and distribution of NMN is regulated to fuel the NAD+ biosynthesis in different tissue.
In the manuscript published in 2019 in Nature Metabolism, we employed several biochemical and in vivo (testing done in a whole organism) analyses to demonstrate that the Slc12a8 gene encodes a selective NMN transporter that facilitates the direct uptake of NMN into cells and intestinal tissue of mice.
We found that Slc12a8 is regulated by NAD+, specifically, Slc12a8 expression is increased when intracellular NAD+ levels are declined, as a compensatory mechanism, in order to maintain the cellular NAD+ homeostasis.
The Debate Around Slc12a8
LB: Proponents of alternative NAD precursors (NAD biologist Dr. Charles Brenner amongst them) such a Nicotinamide Riboside have contested that slc12a8 is an ‘intestinal cation-calcium transporter’ and not an NMN transporter.
The NMN proponents predicted that NMN would still work as NMN in cells that don't have NR kinase but we and others showed that when NR kinase is knocked out, NMN can only raise NAD+ by acting as nicotinamide. That's because NMN works by conversion to NR and needs NR kinase /14
— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020
Surely the ‘devil in the details’, but what is your reply to such claims?
How can we trust that NMN is making it ‘into the cell’ intact, rather than only through the Nicotinamide Riboside Kinase pathway as NR?
AG: Slc12a8 is an orphan member of the SLC12 family of the electroneutral cation–chloride co-transporters, this means that so far, its function as cation–chloride co-transporter has not been demonstrated.
Indeed, Slc12a8 shares low level of similarity with its family members for what concerns amino acid sequence and predicted membrane topology.
As described in our Nature Metabolism paper, we have conducted isotopic tracing experiments using side by side isotopic NMN and nicotinamide riboside in Slc12a8-OE NIH3T3 cells (the cell line overexpressing Slc12a8 protein) and primary hepatocytes from Slc12a8 knockout mice (mice completely lacking the Slc12a8 protein).
Both experimental conditions demonstrate direct NMN uptake without any previous conversion of NMN to nicotinamide riboside outside of cells.
LB: Thanks for answering that very important question.
NMN as a Topical Cream for Skin Health
LB: Moving on from transporters, and onto Elevant’s impressive research efforts, you are engaging with some very significant topic areas - namely beauty and sports performance, which are very significant consumer markets.
Could you share with us the future of NMN based ‘creams’ for topical use? Is this a future development area for beauty products? And do we know if NMN can enter skin cells through a topical? (We are very interested in measuring & preserving aesthetic age)
AG: Yes, previous research has shown that NAD+ appears to play an enormous potential role in skin health.
Research has shown that NAD+ energizes aging skin cells to function more like young cells, counters transepidermal water loss and improves the moisture content of the outer layer of the skin, along with several other actions that support healthy skin.
We have conducted clinical trials that have directly shown the beneficial effects of NMN on the skin.
The trials demonstrated improved skin moisturization, elasticity and brightness, and a reduction in skin roughness and visibility of wrinkles. The results are to be published soon and we will share them with you.
NMN for Exercise Recovery
Longevity Blog is very interested in how anti-aging compounds might improve athletic performance and the benefits of exercise.
Another longevity supplement “Urolithin A”, which is derived from pomegranates, also has benefits on improving physical recovery, through the mitophagy pathway. Read more!
LB: An ongoing clinical trial is now recruiting participants, which will analyse the benefits of NMN for ‘physical capacity and recovery’.
Looking forward, do you see a potential future role for NMN in human performance (i.e. sport)? If so, do you have any insights on how it might improve an athlete’s ability to compete in their sport of choice?
AG: We have preliminary results showing NMN is efficient on physical recovery, at any age. We will keep you informed, prior to the publication of our results.
Upcoming NMN Clinical Trials
LB: Beyond these two clinical trial areas, Seneque are also ‘preparing’ several more clinical trials covering many areas with NMN-C: impact on NAD+ levels, NMN vs NR, sleep, cognitive function, immunity - each is a significant undertaking (self-titled ‘the world largest pipeline’).
What timeline do you expect for the results on these projects? They will each go quite a long ways toward demonstrating the efficacy of NMN supplementation.
Seneque has a very impressive pipeline of NMN based clinical trials at various stages of maturity. Find the latest on their website.
AG: Two more studies started this month (May 2021), a tolerance and a pharmacokinetic study with 20 participants each and dosage of 400mg per day. Preliminary results to be announced next July (2022).
The first results of further trials will be published Q3 2021 and several publications will occur until July 2022. You can see our extensive clinical research pipeline here.
Some additional confidential studies are being conducted at the moment, so pending the timing and results of those we hope to start communicating about them at the end of this year.
We are confident it won’t be long until we can demonstrate the efficacy of NMN supplementation in several clinical trials.
We aim to be able to share results sometime between Q3 and Q4 2021.
Research Business Partnerships for Longevity Research
“We are confident it won’t be long until we can demonstrate the efficacy of NMN supplementation in several clinical trials”
LB: Some elements of these clinical trial efforts will occur in partnership with the Buck Institute, namely the pre-clinical studies and basic research efforts.
Could you describe the merits/value of private longevity technology companies collaborating with leading aging research institutions? What are the challenges for you personally, ‘wearing two hats, so to speak (as you’re also a scientist at the Buck Institute)?
AG: The main interest in collaborating with leading aging research institutions is to work and share knowledge with scientists coming from various backgrounds and expertise, foster new ideas and drive our research to constantly innovate.
This allows diverse new research leads and areas of study, all undertaken in line with scientific principles.
The powerful and high-end equipment and infrastructure at the Buck is of course a huge asset.
Finally, as you know, time is of the essence. These partnerships allow invaluable gains of time.
NMN-C is Manufactured to a High Standard
LB: Elevant is now manufacturing NMN-C in Europe, which differentiates from other suppliers of NMN, who rely on manufacturing in China. This undoubtedly introduces additional costs, but likely as a trade-off for many benefits.
Could you comment on what ‘Made in Europe’ means for consumers?
AG: We strictly control every element of our proprietary manufacturing process, which we undertake at cGMP-certified facilities in France. Consumers receive what we believe are pharmaceutical grade and the highest levels of quality and safety available in an NAD+ booster today.
Dr Grozio’s Longevity Strategy
LB: Dr Grozio, changing gears, as we close off the interview - could you share with our audience one or two items from your personal longevity strategy?
AG: I am Italian, therefore I am following a Mediterranean diet, rich in vegetables, legumes, fish and extra virgin olive oil.
Moreover, I am taking our NMN-C every morning to boost my physical and mental energy needed to go throughout the entire day.
LB: Dr. Grozio, thank you such much for taking the time to answer our equations today!
Want more NMN Focused Content? We got it!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Biological Age Testing with Glycans - Glycan Age
Should you try a Glycan Age Test?
The GlycanAge test kits - a clean, elegant design with fascinating technology under the hood.
This trend is in its early stages, but is set to continue, as gathering detailed information about your body to assess how quickly it is ageing hits the mainstream.
Today, we are introducing you to a new way to assess your biological age.
Whereas previous methods we have reviewed use age-related blood markers or your epigenome for this assessment - today’s technology from GlycanAge uses your glycans.
What are Glycans? Glycans and Biological Age
To start things off, we should probably address your first likely question - what the heck are glycans?
Clearly we need to understand this a bit first, before we can understand how they can be used as a biological age measurement.
Glycans is not a term that most people are familiar with, but they actually refer to a fairly simple concept.
First, we start with monosaccharides, which include more commonly known ‘sugars’ including fructose, glucose, and galactose.
Most of us are familiar with these monosaccharides - they are the simple carbohydrates common in our diet. More broadly, they can be thought of as the ‘fuel’ for our cells, as well as the energy source for most biological organisms!
use the code “LONGEVITYBLOG” at checkout to save 15% on GlycanAge tests
Glucose Molecule (Monosaccharide)
Fructose (Another Monosaccharide)
Combining Monosaccharides to Create Glycans
In practice, monosaccharides can actually be linked together in a very wide variety of long chain-like formations. This how you create a glycan.
A very well known glycan (also known as a polysaccharide) is cellulose, take a look at how it is built out of the monosaccharides above, just in a much more complex arrangement.
Cellulose - a combination of glucose molecules to form a glycan
Glycans and information
Glycans are influential in many processes occurring within your body. One way to think of their involvement is carriers of information.
As complex arrangements, there are many unique arrangements of glycans in the body which often represent very important signals regarding your health and wellbeing.
A healthy cell, with healthy glycans at the cellular membrane (the multi-coloured squares, circles and lines). Credit: Gly-tech
The valuable ‘signal’ that these complex sugar structures can offer has resulted in the field of ‘glycoscience’, which studies wealth of information glycans have to offer.
This information includes critical details about your overall wellbeing, with the presence (or absence) of certain glycans can be indicative of many conditions in the body, including many diseases, as well as - you guessed it - the processes behind ageing itself.
Glycans, Inflammation and Ageing
An unhealthy cell, with unhealthy glycans at the cellular membrane. Credit: Gly-tech
Glycans are intimately involved with your immune system, where they are used to ‘tag’ invading pathogens, signalling the immune system to attack and remove them.
Furthermore, the wrong glycans in the wrong place can generate an immune response, which then drives inflammation.
If you’ve learned about the basics of aging, and many of you have, you’ll be quite aware of the importance of tracking and managing inflammation to stay healthy for as long as possible.
The link between inflammation and ageing is known as ‘inflammaging’.
Dive deeper? Read more about inflammaging straight from the source in this very important 2014 paper which established the concept.
High level overview: Inflammaging is the process whereby increasing levels of inflammation add continual age-related stress and damage to the body, including more inflammation - and thus a feedback cycle develops making you age even faster.
Sounds like a great thing to keep in-check, no?
The links between inflammation, aging, and glycans are what make glycans great choice for monitoring your biological age.
GlycanAge as a Biological Age test
While glycoscience still has much to learn about glycans and their role in aging, metabolism, disease and immune function, there are many decades of research and enough large datasets available to support the creation of a biological clock based on glycans.
We’ll be covering the specifics on how this works in upcoming posts, but the key takeaway is: tracking the characteristics of the glycans in your body can provide an accurate and valuable assessment of your biological age.
And in the case of GlycanAge, your biological age will be primarily influenced by four lifestyle factors:
Stress levels
Exercise load (both too little and too much)
Dietary choices (including food allergies)
Sleep (what’s the right amount for you?)
Each of these factors are known to be very influential in how you are ageing.
As such, you can use a GlycanAge test to create a baseline, before making controlled changes/improvements in these factors, and then re-testing to see if they worked (i.e. did you reduce your biological age?).
This is central to what Longevity Blog is all about - self-experimenting and customising your own longevity strategy to make the best gains in your healthspan.
Given the nature of these lifestyle factors (stress, diet, exercise), self experimenting with GlycanAge is a very accessible way to start working to improve your own biological age.
Regularly testing GlycanAge can therefore be used to monitor and improve your health over time, with each of those small changes adding up to positively impact your longevity significantly over time.
GlycanAge and Its Mission
Don’t miss it!
We’ll be interviewing glycan expert Gordon Lauc on how you can used GlycanAge to improve your own health & longevity. Subscribe to get notified when we do!
The concept of using glycans to track and positively impact your healthspan has only been made possible through the vision and ambition of GlycanAge’s CEO and Founder Nikolina Lauc
Founded in 2016, the company is built upon the foundational work carried out by expert in all things glycans Professor (and Nikolina’s father) Gordan Lauc.
But don’t take it from us - hear it straight from Nikolina herself:
GlycanAge Founder and CEO Nikolina Lauc
Describe your motivations for founding GlycanAge - what opportunity did you see?
Nikolina Lauc (NL): GlycanAge originally came out of pure scientific curiosity.
My father is a glycobiologist who's worked in the glycan research field for 30+ years, they saw that glycans change with age and were curious as to how and why they change, as well as what we can do to influence it.
Hence the term GlycanAge, actually “GlycanBioAge” originally, was coined.
Glycans are one of the key regulators of our immune system, they contribute to ageing through a process called inflammageing.
Inflammation is a key driver of almost all chronic conditions and glycans are known to change before onset of symptoms and even a decade before onset of disease, giving us an opportunity to do true prevention and extend one's healthspan.
“Glycans are known to change before onset of symptoms and even a decade before onset of disease”
How would you describe GlycanAge’s mission - what drives your team? What have you set out to achieve?
NL: We want to keep you and your loved ones around for longer through precision health.
Our mission is to bring glycoscience into the hands of both clinicians and consumers to inform, guide and preserve your future health.
Glycans have a large influence on your unique biology, they play an intermediary role between your genetic potential and end phenotype, their true value lies in uncovering which intervention or lifestyle works for you particularly as an individual.
How has regularly testing your own GlycanAge improved your wellness?
“Glycans true value lies in uncovering which intervention or lifestyle works for you particularly as an individual.”
NL: Although my GlycanAge has always been favourable, regular testing helps me measure the damage (for example - COVID lockdowns and weight gain), and get back on track through sustainable change.
Beyond me, I've probably tested the majority of my extended family!
Coming Up:
(1) An interview with GLYCAN expert Gordon Lauc (read that here!)
(2) How our Founder Nick is using GlycanAge to run his own self-experiment (read it here)
Follow our Founder Nick on Twitter for the latest #Longevity news!
-
RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
-
My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
-
It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
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“The #longevity segment opened my eyes to the groundbreaking advances in biotechnology, health, and wellness. The i… https://t.co/F8YB7PAeMW
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I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
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Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
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RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
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Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
Nick also posts related #Longevity content to Instagram as well, follow him at @nickengerer
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN Nicotinamide Mononucleotide Before and After
NMN Before and After with Biological Age
In mid 2020, I set out on a self-experiment with NMN. The purpose of this experiment was three-fold
First - my primary intention was to lay out some suggestions for how you could structure your own self-experiments, and not just for NMN
Second - I of course was quite curious what my own results would be, and wanted to have a well-controlled self-experiment to answer the question: should I continue to invest in NMN as part of my longevity supplement stack?
Third - to raise awareness of NMN, biological age testing and encourage more of you to join in on being a biohacker!
Designing a self-experiment with NMN in mid 2020 was a unique challenge, as at the time, there was no direct way to test intracellular NAD levels.
That has however changed, and in upcoming posts, I am going to show you how to test your NAD levels directly. If that sounds interesting, be sure to subscribe below!
Takeaway: Over 6 months, a combination of 500mg NMN, 500mg TMG and 500mg resveratrol improved my biological age by 3.5 years. Read on to learn more!
Use the code ‘longevityblog’ to save 10%.
Looking for an NMN supplier? I recommend DoNotAge, who:
offer a third party tested product
have a bulk supply option (100g)
offer further savings when you subscribe to regular shipments
plus I can get you a discount: Use the code ‘longevityblog’ to save 10%!
Self-Experimenting With NMN
It is not easy to run a self-experiment. To review, all self-experiments are:
Difficult to control
Often hard to measure directly
Prone to bias and placebo effect
Even when well-controlled, don’t necessarily provide clear insights
Let’s take a minute to address each of these, how this particular self-experiment addressed each over the course of the 6-months of NMN supplementation.
Control
Over the course of my 6-month experiment, I made several efforts to control the experiment:
My exercise ‘Load’ as per my Garmin Fenix 6 Pro, which I use to track all of my workouts. At top, near the start, at bottom, near the end of the 6 month period.
I did not change my exercise load or volume
I did not change my diet
I did not start taking any other supplements
I did not make any other major lifestyle changes
It is of course not possible to completely control your life! However this does not mean you should not try.
Of these items, I would suggest that consistency in diet and supplementation are of paramount importance.
You can find many “NMN before and after” testimonials on YouTube, for example, but each of these has many problems with control.
The most common issue is making too many changes, mostly around supplementation protocol, during the ‘before’ and ‘after’ period.
Your chief goal here is to decide: is taking NMN worth my hard earned cash?
You can’t make that call if you’re also introducing many other longevity supplements at the same time! You’d be surprised how often this is the case! Be patient and be consistent.
Measurement
In the absence of a direct NAD test, the decided measurements before & after were set according to the 2x clinical NMN trials which were ongoing at the time, as well as adding biological age:
Lipid profile
Blood pressure
Biological age
Epigenetic age (Saliva Test via Chronomics)
Phenotypic age (Blood Test)
Bias & Placebo
I put serious thought into how to conduct a double-blind experiment, but ultimately elected not to.
Given the objective measurements we could draw from the above, and the ‘n of one’ experimental design, this was not practical to implement.
It also reduced the likelihood that everyday folks like yourself would be able to repeat the experiment effectively.
In the effort to minimise placebo effect, I made it my mindful intention to not overhype my personal attitude toward the experiment.
To be quite honest - I adopted quite a sceptical attitude.
Personally, I was unconvinced that NMN would make much of a difference in my day-to-day experience, as there was relatively little science in human subjects & most of these ‘hot trends’ turn out to be over-hyped!
NMN
NMN Self-experimentation Protocol
The supplement protocol for this self-experiment was designed to match the widely used combination of NMN, Resveratrol and TMG:
NMN at 250mg/day (first two months), 500mg (following four months)
For risk management, 1:1 dosage of Tri-Methyl Glycine (TMG)
Resveratrol at 500mg/day, taken with a high fat meal
Note: this was not a change for me, I’d been taking it for 2+ years, and therefore did not interfere with the need for supplemental control
NMN Before & After: Our Hypothesis
This experiment was undertaken to test the following hypothesis (all self-experiments should have one!):
NMN supplementation will boost intracellular NAD+ levels
Boosting NAD+ levels with NMN will measurably improve select characteristics of youthfulness
Combining boosted NAD+ with a sirtuin activator (resveratrol) will enhance DNA repair
Combined, these effects are hypothesised to be likely to:
change blood lipid profile (as per clinical trial designs)
change blood pressure (as per clinical trial designs)
slow or reverse biological age (Longevity Blog hypothesis)
NMN Before & After: Results
The self-experiment was run from 1 August 2020 for 6 months until 31 January 2021.
What follows are the results, including both hard data points and anecdotal observations.
Blood Lipid Profile:
Blood lipids refer to the commonly assessed HDL, LDL and Total Cholesterol measurements. These are also joined by Triglycerides to form the ‘Blood Lipid Panel’ of tests.
As you can see in the provided image, there was no significant change in any of these parameters over the course of my NMN self-experiment.
Blood Pressure
Blood pressure measurements at the start of the experiment were ~125/85.
At the end of the experiment, 126/84.
There was no significant change in blood pressure from the NMN self-experiment.
Biological Age: Phenotypic Age
Phenotypic age is calculated using 9 blood based biomarkers, to calculate a biological age.
This is based on work led by Yale researcher and longevity thought-leader Dr. Morgan Levine (whom we hope to interview on the blog in the future!).
We’ve previously reviewed this test, including providing information on how you can use it yourself here (its free!).
Blood markers in this test include:
White Blood Cell Count (WBC)
Red Cell Distribution Width (RDW)
Mean Corpuscular Volume (MCV)
Fasting Blood Glucose
Lymphocyte %
Creatinine
Albumin
Alkaline Phosphatase (ALP)
C-reactive protein (CRP)
If you’d like to learn more about any of these blood markers, checkout Lab Tests Online.
Pictured: My Phenotypic Age (Biological Age measure #1) over time.
At the start of the self-experiment, my Phenotypic Age was 28 (Chronological Age 34).
At the end of the self-experiment, my Phenotypic Age was 25 (Chronological Age 35).
Given that 6 months passed, this equates to a total change of -3.5 years of Biological Age.
Did I reverse my biological age with NMN?
Now - the key question is, was this change significant? Was it due to the NMN based protocol?
This comes back around to one of my initial opening points about self-experiments: “Even when well-controlled, they don’t necessarily provide clear insights”
For our analysis, we should extrapolate from the baseline measurements a bit further.
Over the preceding 3 years, my Phenotypic Age was an average of 25.7 years old. It was as high as 28 and as low as 23.
More importantly, we need to consider the difference between biological age and chronological age.
My average difference between biological age and chronological age over the preceding 3 years was -7.7 years. This was as high a -10 years and as low as -5 years.
At the start of the NMN self-experiment, this difference was -7 years (below the average), whereas at the end, it was -10 years (at the previous extreme).
There is a degree of subjective interpretation which must occur here, as the data volume does not lend itself to statistical analysis.
Based on the data and trends, there is sufficient evidence to suggest that this NMN based protocol reversed my biological age.
It is however is not conclusive evidence, and as a scientist, I choose to approach that statement conservatively.
There is a bit more to explore however, to let’s continue.
Biological Age: Epigenetic Age
This one was a real bummer. My follow-up test with Chronomics failed their quality control step, meaning the biological age result was not valid.
This was a crushing blow, as it was the chief data point, in my opinion.
However, I have re-tested it, but it was not in-line within the 6-month period self-experimentation period.
Due to my choice to begin another 6-month self-experiment immediately following this one, the next biological age result will not be valid for this experiment.
I’ve since dramatically increased my exercise routine (I’m now training for triathlons), made major dietary changes and increased my NMN supplementation to 1000mg/day in a separate 6-month self-experiment aimed a direct feedback from Chronomics on how to reverse my biological age.
I will update this post with those results, when they are returned, however they will not be well-controlled for NMN experimental purposes.
I know - major bummer! 😔
Such is self-experimenting life!
NMN Before and After: Anecdotal Observations
SF-36 Questionnaire
My results from the SF-36 questionnaire before & after did show a slight change in a few key areas.
While I did not experience any changes in general health, physical health problems or limitation of activities, I did have interesting results in the energy & emotions section.
Excerpt from my SF-36 questionnaire, before and after the NMN self-experiment.
At the start of the self-experiment, I think I was feeling many of the things that folks in their mid-30s start to feel. Notably less energy than in their 20s, less upbeat and more likely to feel worn out at the end of a long day.
Over the course of the self-experiment, this changed in notable ways, in a sustained way that continues to today.
You can see for yourself the meaningful parts of the questionnaire that changed for me in the following image.
I have to add - it is completely possible that these results are placebo based. I was taking NMN, most folks who supplement with NMN boast ‘increased energy levels’.
But of course, since NMN is hypothesised to impact intracellular energy, this is what we expect to happen.
When it comes to ‘energy levels’, NMN is a prime placebo influence candidate.
Nicotinamide Mononucleotide Before and After Conclusions
To summarise, I was able to run a well-controlled self-experiment with NMN supplementation at 500mg/day.
I recorded before and after blood tests, blood pressure and detailed subjective experience related data.
Initial results do indicate improvement in my Biological Age (as per the Phenotypic Age) by approximately 3.5 years.
Subjective data (qualitative data) support this quantitative data, and therefore the conclusion is: NMN left me both feeling younger and perhaps biologically younger.
However, this cannot be placebo controlled, and warrants further testing. In particular, direct testing of NAD levels is now available, and that is what I will be testing next!
Also, we have not been able to test the much more robust and accurate epigenetic age via Chronomics, which was unable to be measured. Ultimately, this was the most powerful data point, and though disappointing - we will revisit it.
Coming soon, I will review the results from testing intracellular NAD levels directly, before and after 1000mg of NMN.
Follow NICK on Twitter for the latest #Longevity news!
-
RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
-
My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
-
It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
-
“The #longevity segment opened my eyes to the groundbreaking advances in biotechnology, health, and wellness. The i… https://t.co/F8YB7PAeMW
-
I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
-
Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
-
RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
-
Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
NICK posts related #Longevity content to Instagram as well, follow HIM @nickengerer
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN-C, Elevant and the future of NAD boosters: An Interview with Dr Eric Verdin
NAD Precursor NMN-C - A New NMN Supplement
As we have discussed in recent posts on NAD boosters, clinical trial data for NMN in humans remains quite limited.
In fact, up until recently, it wasn’t even well established that NMN was safe to use as a supplement. Hence, why we’ve had to discuss this issue and how minimise any risks in involved should you choose to self-experiment with NMN.
One key outstanding question has been - is NMN safe to take as a supplement?
IS NMN SAFE?
Excitingly, this question has now been answered, thanks to innovative work by the company ‘Elevant’ (in collaboration with two other parties, more on this shortly), who recently published results from a toxicology study for NMN supplementation (read it here).
On the back of this successful study, Elevant is now offering this a novel form of NMN, matching that which was used in the research effort - the product is called ‘Prime’, and the specific NMN formulation is called NMN-C.
What is NMN-C?
NMN-C is differentiated by its quality and extremely high-level of safety where the processes for characterising and removing as many potential impurities has been standardised and follows pharmaceutical grade guidelines.
Elevant’s NMN-C product, “Prime”
There are not any changes to the molecular structure, rather NMN-C is the outcome of this highly rigorous processing approach.
This outcome of this method for producing NMN has then been tested at high dosages (i.e. the study we just mentioned) and also in pre-clinical testing in humans.
This has made NMN-C the only form of NMN to be categorised by the US Food and Drug Administration as “Generally Recognised as Safe” - so called GRAS status.
Elevant, Seneque and the Buck Institute
These recent efforts to create and study NMN-C are the fruits of an exciting trifecta of collaboration between Elevant, its parent company Seneque and the Buck Institute.
They have an exciting pipeline of future NMN related studies in humans, including skin health, muscle recovery and more. We’ll explore these topics in an upcoming post with Elevant’s Chief Scientist.
Together, these companies boast some very grand visions, which should get any longevity enthusiast (that’s you) quite excited.
The Buck Institute for Research on Aging is a global leader in the study of aging, and increasingly, interventions in age-related disease.
Seneque, the parent company of Elevant, is a Swiss life sciences company, founded by French entrepreneur Guillaume Bermond, who now leads the company on its mission to “increase healthspan by 20% in the next decade”.
Rounding out the three-way collaboration is the Buck Institute for Research on Aging, who are global leaders in the study of aging, whose missions is equally grand - “to end the threat of age-related disease for this and future generations”.
Interview with Longevity Pioneer Dr Eric Verdin
Playing a key cross-over role between these three entities, is Dr Eric Verdin, CEO and President of the Buck Institute, and more recently, Chair of the Scientific Advisory Board at both Seneque and Elevant.
Longevity Blog reached out to Dr. Verdin to discuss this new role as at Seneque, and in order to better gauge his view on the promise of NMN supplementation in humans.
We discuss the use of NMN in human subjects, the role of inflammation and CD38 in NAD biology, the future of NAD boosters and even his personal longevity strategy.
This interview was conducted in written format over email correspondence during May 2021
Does NMN actually work? Is NMN effective?
Longevity Blog (LB): Clinical trial data for NMN supplementation in humans is at a very early stage, and we’ve yet to see conclusive results. Yet, the new venture Seneque will deliver NMN based products. What gives you confidence in the efficacy of NMN supplementation in humans?
Dr. Eric Verdin (EV): That’s a great question. I think that one should know that not everything from mouse or from animal model experimentation will actually translate into humans, and so there is always some degree of uncertainty in terms of what will happen.
Most NMN research has been performed in rodents, what will this mean for humans? Image credit
However, there is now growing evidence that NMN supplementation in animal models really has profound effects in the biology of every organism on which we have tested it. Based on this, one can be reasonably optimistic that we’re going to be seeing the same thing in humans.
One key thing that we will have to consider is the dose at which we give the NMN. Right now, NMN is typically commercially available at lower concentrations than what we’ve given to animals, and eventually we will have to account for some of the potential differences.
“NMN supplementation in animal models really has profound effects in the biology of every organism on which we have tested it”
CD38 Inhibitors for NAD Boosting?
LB: One of the more recent discoveries related to NMN supplementation, is a need to pay attention to the role of the CD38 enzyme. The Buck Institute recently published a study on the role of inflammation and macrophages in CD38 regulation. Could you comment on the potential role of CD38 ‘inhibitors’ alongside NMN supplementation? What compounds might prove useful in this role?
EV: Yes. What this paper actually showed is that, as we age, the activity of this enzyme called CD38 increases. CD38 is an NAD hydrolase, and so it is able to take NAD and to cleave it into its byproducts – ADP-ribose and nicotinamide – and we think that it is one of the major pathways that leads the progressive degradation of NAD that occurs during aging.
Longevity Blog did a deep dive on CD38’s role in NAD biology with Nuchido Founder Dr. Nichola Conlon - be sure to check it out!
So, on this basis, one hypothesis would be that to restore or maintain NAD levels in aging, we have to inhibit CD38, but you also have to replenish depleted NAD levels.
This is where NMN could come in. One thing to also consider is that CD38 also cleaves NMN, so this makes it even more of an important potential synergy between providing inhibitors of CD38 and providing NMN.
I think this is one way to move forward into the future – to have specific CD38 inhibitors and also to provide NMN to restore NAD levels.
“one hypothesis would be that to restore or maintain NAD levels in aging, we have to inhibit CD38”
Chronic Inflammation: CD38 and Senescent Cells
LB: As a follow-up, given the role of chronic inflammation and senescent cell activity (SASP) to create pressure on NAD levels in the cell, does this suggest that senolytic compounds (e.g. fisetin, quercetin, etc) may be a natural partner in boosting cellular NAD levels in addition to NMN?
EV: That’s a very good question. In the paper you discussed just before, which we published last December in Nature Metabolism, we identified the mechanism for the progressive increase in CD38 during aging, and one of the mechanisms was the progressive accumulation of senescent cells.
As a part of the ageing process, CD38 and Senescent cell activity both increase, lowering NAD+ levels. Image credit: Buck Institute
The senescent cells secrete a series of pro-inflammatory cytokines, the so-called SASP, which means ‘senescence associated secretory phenotype’.
What we showed is that the SASP is one of the mechanisms by which CD38 increases during aging.
Based on this, one could predict that if we were able to eliminate a senescent cell, we would eliminate the SASP and then we would eliminate the induction of the CD38 expression.
One thing to remember is that the SASP is not the only mechanism that was responsible for the induction of CD38. There were other substrates including bacterial products such as LPS (lipopolysaccharide), and other series’ of factors that we will also have to control.
So I believe that fighting the induction of CD38 is going to be harder than inhibiting CD38 expression or providing NMN as an exogenous substrate.
“if we were able to eliminate a senescent cell, we would eliminate the SASP and then we would eliminate the induction of the CD38”
NAD Boosting Supplements: More Options on the Horizon?
LB: With a forward looking approach on NAD boosting, NAD precursors and their role in alleviating some of the pressures of aging, do you believe we are likely to see a wider variety of NAD boosting supplements emerge over the next 5-10 years?
If so, what form might these (strategies) take? The recent discoveries around the reduced form of NMN (NMNH) is one such example.
EV: This is a very good point, and one I think is exciting. Clearly, what the data shows is the interconnectedness between multiple processes is something that we had actually not fully appreciated.
One is NAD degradation, that’s the role of CD38. The role of senescence. The role of what we call the PAMPs (pathogen associated molecular phenotypes) such as LPS and others.
So, if you think about fighting aging and its manifestations, I would predict that in the future, we will likely have a combination of these approaches to really maintain NAD levels, to eliminate senescent cells, and to restore NAD levels, using a variety of precursors.
“I can predict, based on what has been published and what we know, that there will be other [NAD boosting] molecules.”
Right now, the field is focusing on NR (nicotinamide riboside) and NMN (mononucleotide nicotinamide). Both of those have shown remarkable activities, which is why there is so much excitement in this field.
But I can predict, based on what has been published and what we know, that there will be other molecules.
One thing that is really important to realize is that to be truly demonstrated as efficacious, I think it will be important for these molecules – whatever they are, whether they are CD38 inhibitors or NAD precursors – we need to conduct clinical trials to make sure that whatever we’re giving to patients is not only given at the right dose, but is safe and actually has the intended safety profile and the intended benefit.
I think this is the way that truly evidence-based medicine has been progressing over the last 100 years and I hope that our field of aging research will abide by this principle and demonstrate the efficacy of what we’re providing to patients.
Wearing Two Hats: Bridging the Gap Between Ageing Research and Deploying Interventions
LB: Dr. Verdin, could you comment on the importance of translational roles, such as your role as Chair of the Seneque Scientific Advisory Board, in bridging the gap between ageing research and making relevant treatments available to the general public?
While keeping a foot in both the ‘research’ and ‘commercial’ camps can be difficult to navigate, surely they are likely to become more common as this field matures?
EV: I am very excited by the ongoing opportunity and ability to not only conduct basic research and make discoveries – that’s been my whole life’s work.
But as I’m getting older I have been increasingly interested in taking things one step further and really pushing the envelope to make these discoveries closer to translation in humans.
This is certainly the approach we’re taking at the Buck Institute. We’re starting companies, we’re collaborating with established pharmaceutical companies, we’re collaborating with biotech companies such as Seneque.
I very much view my role not only as Director of a basic research institute, but as an advocate for pushing these discoveries into the clinics. And I really think the science is there in terms of the promise.
“I hope that in 20 years from now, we’ll look back at the Buck and say that this was an institute that really took the bull by the horns and really tried to change the way we age”
The deep questioning and the hard work start now. Which is to say really bring this into humans. We know from data in the pharma industry that it is much harder to translate into humans, especially given the diversity of the human population both in terms of genetics and lifestyle and so on.
One of the reasons we work closely with Seneque is the value they place on proper clinical research. They have a significant program of clinical trials in play which will drive the understanding of the effects of NMN in humans for all of us.
Seneque’s mission is to increase healthspan by 20% in the next decade.
In the future we will hopefully see that in some way the Buck successfully redefined what the basic research institute is doing.
In this case we are aggressively building a translational infrastructure – by collaborating with pharma and biotech and also by starting our own company.
I hope that in 20 years from now, we’ll look back at the Buck and say that this was an institute that really took the bull by the horns and really tried to change the way we age, not only in animal models but in humans. I think this is a little different from what most places do, but I find it very exciting.
“As I’m getting older I have been increasingly interested in taking things one step further and really pushing the envelope to make these discoveries closer to translation in humans.”
Dr. Verdin’s Personal Approach to Longevity. Does Dr. Eric Verdin take NMN? What supplements does Dr Verdin Take?
LB: Dr Verdin, changing gears, as we close off the interview - could you share with our audience one or two of your personal longevity strategies?
EV: I have to be careful here, because these are not ‘recommendations’, this is strictly what I do as a person. I believe in lifestyle effect being very critical in determining longevity, so I really focus on five different aspects.
Nutrition & Fasting
One is nutrition, with a focus on intermittent fasting. Every three months, I do a week of fasting. I do time-restricted feeding, which means I eat for about eight hours of the day and do not eat for the remaining 16. So that’s pillar number one – nutrition.
Exercise
Pillar number two is exercise. I try to fit in between one and two hours of exercise every day. I think it is the best and safest anti-aging medicine that we have today, and it will remain so for a little while longer, until we discover better medicine.
“I used to be an every-day-one-glass-of-wine drinker. I have seen how much this alters the quality of my sleep and I would now define myself as an occasional rare drinker.”
Sleep
The third pillar is sleep. I think we live in a society that is chronically sleep-deprived. I try to sleep a good amount every day and try to make sure it’s good quality by mitigating all the factors that I’ve discovered actually interfere with my sleep.
I use an Oura ring and the Whoop, which are two wearable devices that allow you to closely monitor your sleep and which have allowed me to determine what the factors are that affect the quality of my sleep.
One of the ones that actually surprised me was the effect of alcohol. I used to be an every-day-one-glass-of-wine drinker. I have seen how much this alters the quality of my sleep and I would now define myself as an occasional rare drinker.
Stress Management
The last thing is stress. I really believe that stress is a significant contributor to aging, so I try to mitigate my stress by doing yoga, by meditating when I have the time and really try to mitigate the factors that stress me. For me, exercise is probably the best anti-stressor.
Supplement Routine
In terms of supplements, I believe in measuring whatever can be measured in your blood.
There are number of companies that provide this type of services and in correcting what seems to be off-balance. So I take a number of supplements, simple ones like vitamin D and vitamin B12.
I also take NMN every day. Having taken it myself at significant doses, I really see the effects, so I’m encouraged to continue.
I take metformin for two reasons. First, it’s been shown to have many properties as an anti-aging medicine. But also my fasting blood sugar was borderline and I thought that, given my age, there were little risks in taking metformin.
So there you are – the pillars of my health or longevity program at this point.
LB: Dr. Verdin, thank you so much for taking the time to answer our questions. It is a true privilege to hear from one of the aging’s sectors most notable and well respected leaders.
Looking for more NMN based content? Look no further
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Choosing an NMN Supplier for Self-Experimentation
What is the Best NMN Supplement?
Who should you choose for your NMN supplement?
Fast-take: I recommend DoNotAge, who offer a third party tested pure product, have a bulk supply option (100g) with further savings when you subscribe to regular shipments. Use the code ‘longevityblog’ to save a further 10%!
Want the details and the ‘why’ I make this recommendation? Do read on!
Today on Longevity Blog, I wrap up my three part series on self-experimenting with Nicotinamide Mononucleotide. Complete with NMN before and after testing.
As discussed in the first post of the series on NMN risk management, there are three key questions that Longevity Blog will engage with on the topic of NMN. These are:
What NMN supplement should I use?
In this third post of the three-part series, we’re going to zoom right in on the question - how do I choose a high quality NMN supplier?
Choosing the best NMN supplement: Potential Pitfalls
NMN is a supplement, meaning its production and distribution are largely unregulated. As such, this potentially exposes the self-experimenter to several potential pitfalls when purchasing.
The most important of which are:
Imposters (i.e. not actually NMN)
Contaminants (e.g. heavy metals)
Impurities (e.g. fillers, extras)
Unnecessarily high cost per dose (e.g. low potency)
Naturally this raises the question - How can we avoid these potential disruptors to our self-experimentation?
For those currently searching for their own NMN supplier, I personally understand where you are coming from.
First up - you are aiming to purchase a product with confidence in knowing it is NMN, but fake supplements are common and are lurking amongst in the available NMN suppliers on the web right now.
Even if you can become confident the product in question is NMN (not an imposter), you still must consider the risk of contaminants such as heavy metals showing up in your supply.
Furthermore, we don’t want to waste our money on a product that has low potency and/or uses fillers to push more product (impurities).
And then there is cost. Once satisfied on the above three - imposters, contaminants, impurities - we still need an NMN supply that fits our budget. This is complicated by varying levels of potency across the options:
what is a ‘dose’?
how much NMN per dose?
how many doses per container?
shipping costs?
The above long list of factors can make selecting an NMN supplier quite daunting, and perhaps overwhelming!
No one individual can take on the challenge of sorting through these points on their own. Thankfully, the NMN self-experimentation community is working together on this one…
NMN Supplement Review Useful Sources
One of my favourite aspects of the self-experimentation community, is the collective spirit of sharing knowledge and helping each other navigate the pitfalls of sourcing supplements.
Despite its relative novelty, NMN suppliers have been usefully reviewed in several formats - the most valuable of which, at this stage, are two YouTube videos.
In the first, we find that once again, my mate Dr. Brad Stanfield continues to be one of the top sources of information on NMN.
In his videos, he reviews several brands - and parallels my above selection criteria - analysing imposters, impurities, contaminants and cost per dose.
Dr. Stanfield’s endeavour to find 3rd party testing data reveals a key resource in our journey to select our NMN supplier.
The second YouTube video is from Vince and his channel “My NMN Experiment”.
Vince has several relevant videos for the NMN self-experimenter on the topic of NMN sourcing, self-experimentation and review of available third party testing.
Of particular use is his video on ‘Testing Heavy Metals” which you can view below:
Choosing the Best NMN Supplier
Use the code ‘longevityblog’ to save 10% on any order with DoNotAge
Amongst the growing number of choices for supplying NMN, is UK based company DoNotAge.
I recently became a strategic advisor to this company, owing to our shared interest in making longevity supplements like NMN widely available.
Simply put, if NMN can deliver even a fraction of the longevity benefits to humans that are observed in mice, then I firmly believe in the democratisation of access to the molecule.
By democratisation, I mean - making it widely available in both supply and cost. Quality is of course pre-requisite.
Before we move on, it is important to disclose that I stand to benefit from the sales of NMN by DoNotAge due to my advisory role.
However, this monetary benefit is modest and frankly, is not part of what motivates me to self-experiment with NMN, nor to recommend the company to you personally.
Instead, what my position as an advisor has allowed me to do is more clearly understand the NMN global supply chain and access certain confidential information about its production, proprietary competitor testing, distribution and profit margin.
Many NMN options are low quality
Through the clarity this position has provided me, I have a heightened level of concern on the practices of many of the other NMN suppliers.
The issues I am now privy to are numerous and commonplace. I am aware of products sold on Amazon, claiming to be NMN, which contain nicotinamide instead (imposters).
Suppliers who claim to be ‘manufactured in the USA’, source their products from China (lack of integrity) and package it in the United States in order to ‘cheat’ their way to this label.
Others have degradation of the product due to poor packaging and storage practices (potency), while many others provide no third party certification regarding heavy metals (contaminants).
Moreover, many sell NMN at low potency, including doses at 50 - 150mg, which are well below even the conservative doses being used in early clinical trials.
DoNotAge is a High Quality Supplier of NMN
In addition to the “insider scoop” on the NMN supply landscape, my advisory position has also provided me with a high degree of confidence on DoNotAge’s Pure NMN product.
I know with certainty it is NMN (not an imposter), is appropriately free of contaminants or impurities, and it is amongst the highest potency options available on the market (500g NMN per capsule).
This combination of factors given me the confidence to personally consume the DoNotAge product, using it in my current NMN self-experiment, selecting it from the ‘Wild West’ of NMN suppliers.
Despite the potential conflict of interest I hold in monetarily benefiting from the sales of this product, it is my hope that this vote of confidence may contribute to your own decision making process.
Simply put - in my longevity journey, I am very disciplined in choosing the supplements I consume! DoNotAge passes all my checkpoints.
Reviewing NMN for Self-experimentation Protocol:
Use the code ‘longevityblog’ to save 10% on any order with DoNotAge
Zooming out from the details of choosing the best NMN supplier, let’s come back to my NMN self-experiment.
I am presently wrapping up week 4 of the protocol, which will run for a total of 6 months.
The experiment will rely on several different data points, one of which is before & after biological age tests from Chronomics, and will wrap up at the end of February.
Unlike many of the other self-experimenters out there, I am holding constant my daily habits, diet and supplement routine, in the interest of generating the most robust scientific outcome.
When complete, I will finalise the results and protocol, in order to support the self-experimentation community.
The self-experimentation protocol is as follows:
NMN 500mg per day (updated)
TMG 500mg, every day (1:1 ratio to support methylation)
All of which is being supplied by DoNotAge.
You can find the relevant DoNotAge products in each of the above hyperlinks.
Use the discount code ‘longevityblog’ to save 5%!
Follow Longevity Blog on Twitter for the latest #Longevity news!
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Self Experimentation with NMN Nicotinamide Mononucleotide
NMN Before and After with Biological Age
Given the introduction of nicotinamide riboside (NR) and more recently nicotinamide mononucleotide (NMN) as supplements over the past four years, many in the longevity community are self-experimenting with these molecules which boost NAD+ levels.
Looking for an NMN supplier? I recommend DoNotAge, who offer a third party tested pure product, have a bulk supply option (100g) with further savings when you subscribe to regular shipments. Use the code ‘longevityblog’ to save a further 10%.
Get the details in Part 3 of this NMN self experiment series
As discussed in the previous post on NMN risk management, there are three key questions that Longevity Blog will engage with on the topic of NMN. These are:
NMN
How can we self-experiment to determine efficacy?
In this post, I’ll discuss how we can self-experiment to determine the efficacy of NMN supplementation. Let’s do it!
NMN Self-experimentation: A first draft “how to” guide
Let’s science this and see what happens
As with any good self-experiment, we should design a solid experimental framework based on the principles of the scientific method.
This has caveats however, owing to our inherent complexity as a biological system.
As you up your self-experimentation game (what a biohacker you are!), you’ll find out that self experiments are:
Difficult to control
Often hard to measure directly
Prone to bias and placebo effect
Important to make repeatable
Through this post and others that follow, we will do our best to continually consider these issues with self-experimentation (an example of this can type of thinking can be seen in previous posts).
In your endeavour to self-experiment with NMN, getting the experiment right is particularly important.
It should be our goal to provide insight to the broader self-experimentation community, and facilitate others to effectively self-experiment so we can benefit from collective knowledge sharing.
So let’s aim to get this right, in the name of science!
NMN Before and After, Our Hypothesis: What are we testing?
After thorough consideration, I believe our hypothesis for NMN supplementation can be summarised as follows:
NMN supplementation will boost intracellular NAD+ levels
Boosting NAD+ levels with NMN will measurably improve select characteristics of youthfulness
This hypothesis is formed upon on a large volume of work around NAD+ boosting supplements such as Nicotinamide, Nicotinamide Riboside (NR) and NMN (nicotinamide mononucleotide), which indicate 1) the importance of NAD+ levels on a plethora of cellular processes, 2) the known decline of NAD+ levels with age and 3) the apparently causal relationship in this drop in NAD+ levels with a wide array of age-related diseases.
It also formulated in such a way that we can test it, by gathering related data and analysing them to draw conclusions.
Does NMN Work in Humans? How We Can Test the Hypothesis:
In order to test our hypothesis, we need to determine:
An appropriate NMN dose for raising NAD+ levels
How we will measure the NAD+ levels
What controls we can apply, and adopt defensive positions against bias/placebo
How much NMN should you take?
In order to determine the appropriate dose for the experiment, I suggest we look to the two FDA approved clinical trials which are currently evaluating NMN safety and efficacy:
You can search for clinical trials on any topic you like at clinicaltrials.gov
Clinical Trial #1: Dosing for participants 40-65 years olds set at 300mg/day
Clinical Trial #2: Dosing for post-menopausal women set at 250mg/day
Anecdotes from elsewhere suggest this a good level for supplementation. Consider this 27 year old who was totally ‘buzzed’ on 500mg/day and this discussion thread for a 34 year old (same age as me at the time of writing) settling on ~250mg day.
Setting the NMN supplementation level should be done based on age and moderated based on one’s experience with the dose (e.g. insomnia, flushing, etc can be inferred to mean one should titrate downwards).
Measure: Data Collection for the NMN Self-Experimenter
From first principles, our goal here will be to measure related biometrics before NMN supplementation, and then again after sustained NMN supplementation. However, the details here are challenging. As, unfortunately sampling intracellular NAD+/NADH levels presents a few issues.
So for widespread, democratised access to NAD+/NADH testing, we face these two barriers:
First, direct testing of NAD+/NADH is limited to professional assay test kits (like this one)
This violates our goal to make the experiment repeatable for other self-experimenters.
Secondly, it turns out they are fairly ‘noisy’ data anyway, making interpretation difficult and making representativeness of the measurement problematic
NAD+/NADH levels change dramatically across the day with activity, eating, circadian rhythm (Interestingly, blood glucose exhibits these same characteristics; which is perhaps unsurprising as they are both part of our body’s ‘energy system’ );
even if we could test it directly, we would also need to sample it semi-continuously (many measurements)
However, given the widespread interest, research funding and commercial development of NAD+ boosters, measuring NAD+/NADH is likely to become more widely available in the near future. My research found at least two promising options,:
Liquid chromatography - “high-performance liquid chromatography (HPLC) to accurately measure the levels of NAD+ in cells and tissues”
A bioluminescent biosensor - “for the rapid quantification of NAD+ levels in biological samples, which can be used either in laboratories or at the point of care”
Establishing an NAD+ Proxy
In science, where we can’t measure something directly, we use a suitable proxy. In atmospheric science, to study the past climate, we can use bubbles captured in glacial ice cores to estimate past CO2 concentrations and global temperatures.
Climate researchers do this because they inconveniently didn’t have thermometers sampling the atmosphere 100,000 years ago. Here, our issue is we don't have the ‘thermometer’ for NAD+/NADH levels yet. So what’s our proxy?
I have spent many hours researching and considering this. It is my suggestion is that we leverage several different biomarkers that are representative of youthfulness as our proxies. The reasoning for this reaches back to the hypothesis and the purpose of boosting NAD+ : to restore youthfulness.
There are a few proxies we can draw from the clinical trials mentioned above, these are:
Walking speed tests
Blood pressure
Lipid profile
I suggest we eliminate the walking speed test, as it is really only valuable in advancing aging or for sedentary individuals. The latter three are widely accessible, so we’ll adopt them.
But I suggest we go a bit further in our assessment of expressing a youthful phenotype, and adopt measurements of biological aging. My reasoning for using biological age (BA) is the following:
BA is our target for longevity optimisation
BA measurement and calculation is accessible to others, therefore can be repeated
BA is a wide reaching measurement of overall bodily youthfulness (that is its purpose)
BA has multiple modes of testing available to us; so we can work with more than one
Epigenetic test kits for before and after the Longevity Blog NMN based planned biological age reversal experiment. Read about what I made this choice!
For the NMN self-experimenter, I suggest the following two biological age computation methods.
The first is the Phenotypic Age test, which I cover in this post.
The second is a biological age test based on measurement of DNA methylation (aka epigenetic age)
While the prior test is a blood test, the latter is direct measurement of methylation at CpG sites in the epigenome.
There is a fundamental connection here between NAD+ levels, which are the ‘fuel’ for the SIRT enzymes which repair DNA and regulate expression of the genome.
In theory, increasing NAD+ levels could improve our bodily ability to regulate the epigenome, so potential improvements could be realised in the epigenetic age.
Epigenetic age kits are also becoming widely accessible very quickly, and therefore are repeatable.
Analysis: How should the self-experimenter analyse their data?
At the most fundamental level, at the very least, one should statistically compare the before & after measurements of our proxy measurements.
An added benefit would be the inclusion of additional baseline measurements from before the experiment begins.
This inherently needs to include some basic corrections for the non-stationary nature of the data. In layperson terms - chronological time is passing over our measurement period.
So the ‘after’ measurements should be corrected in our analysis, considering the amount of time that has passed over the course of the experiment.
Lastly, and perhaps more importantly, we must employ purposeful management of potential confirmation bias.
Anyone who is running an NMN self-experiment and is looking after their longevity wants and likely expects the supplement to work.
Since we know the result we want, therefore we need to be defensive against our bias when we draw conclusions based on this result.
This is particularly relevant for bloggers and social media focussed folks - we inherently want the Ben Greenfield headline to draw clicks and eyeballs.
I refuse to do that to you, and will revisit these issues when we analyse the data and draw our conclusions.
NMN Self-experimentation: What’s Next for Longevity Blog?
We’ve nearly designed our experimental framework, but we’ve not yet discussed the dosing protocol. So here’s what I personally plan to do:
Baseline
Measurements of:
Blood lipids
Blood pressure
Estimation of:
Phenotypic Age (established here)
Epigenetic Age (via Chronomics)
Complete the SF-36 questionnaire
Post Protocol
Measurements of:
Blood lipids
Blood pressure
Estimation of:
Phenotypic Age (established here)
Epigenetic Age (via Chronomics)
Complete the SF-36 questionnaire
So, what will the exact dosing protocol be? It is still in draft form, as I am awaiting potential additional insights from first Chronomics test.
These may provide additional insights on what to add to the protocol to further improve my biological age.
This does step outside of the experimental design for NMN self-experimentation, but let’s delay that discussion until further posts.
NMN Self-experimentation Protocol (DRAFT):
NMN dose will be set at 250mg per day (based on clinical trial dosing levels)
Update: Two months into the protocol, I raised to 500mg per professional advice from a knowledgeable third-party
For risk management, we’ll include 1:1 TMG (as discussed in my last post)
Resveratrol at 500mg/day, taken with a high fat meal (I’ve been doing this for 2+ years)
Inclusion of Resveratrol is based on its role as a SIRTuin activator, which pairs well with NAD+ boosting and potential benefits to the ‘health’ of the epigenome
Will you experiment with NMN? You’ll need a trusted supplier - I recommend DoNotAge, who offer a third party tested pure product, have a bulk supply option (100g) with further savings when you subscribe to regular shipments.
Use the code ‘longevityblog’ to save a further 10%.
Get the details in Part 3 of this NMN self experiment series
Follow me on Twitter for the latest #Longevity news!
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN - Nicotinamide Mononucleotide Safety and Risk Management
NAD boosters are a HOT topic. NMN is the hottest 🔥
One of my favourite ways to analyse the latest health action in longevity technologies is to use Google’s keyword planner and trends tools. They form a great way to track the ‘pulse’ of human interest on healthspan. And as I planned my next upcoming series of blog posts on NAD boosting with NMN and diving deep into epigenetics and biological age, I certainly found plenty of evidence of our collective curiosity on the topic.
Given the introduction of nicotinamide riboside (NR) and more recently nicotinamide mononucleotide (NMN) as supplements over the past four years, many in the longevity community are self-experimenting with these molecules. And while the requisite clinical trials (those in humans which reveal their effectiveness) are still ongoing, it is clear from the data and trends I analysed that these molecules, particularly NMN, are moving into the mainstream. Heck, I’ve even run into many folks in the energy sector (where I run my day job - Solcast), taking NR and/or NMN!
Trends in NMN and NR over time
Here is a great illustration on how the search analysis for NR and NMN have changed over time. While NR got an early boost with the launch of Elysium Health and their product “Basis”, searches quickly returned to baseline within a matter of weeks.
NMN however, after an outstanding boost from David Sinclair’s appearance on the Joe Rogan Experience podcast, and likely supported by Dr. Sinclair’s impressively wide-reaching Lifespan book launch tour, has clearly achieved a wider and more sustained appeal. NMN is clearly the hottest topic in the world of NAD+ boosters, and this is supported further by the search results present in many English speaking countries, with thousands of searches for NMN and related topics each month (and growing steadily).
What is NMN? What are its benefits?
It is hardly my role to explain the basics of NMN and NAD+ boosting supplementation, as that is not the focus of the Longevity Blog (here we focus on decision making, actionable insights). Thankfully however, my mate from across the pond Dr Brad Stanfield (New Zealand) runs a fantastic and educational YouTube channel covering these topics. You should be able to find the resources you need to become more familiar with NAD+ boosting supplementation by watching his videos (be sure to SMASH that like button 😂).
NMN Supplementation: Safety, Strategy, Sourcing
There are however three key questions that Longevity Blog will engage with on the topic of NMN. These are:
Is NMN safe for self-experimentation?
How can we self-experiment to determine efficacy?
What NMN supplement should I use?
In this post, we’re looking into NMN safety and risk management. We’ll come back to #2 and #3 in future posts.
NMN Supplementation: Is it safe? (Key Question #1)
When exploring NMN supplementation safety, there are two important sub-questions to explore:
1) Has the molecule been found to be safe by reputable third-parties?
2) Are there known risks with supplementing the molecule?
NMN Safety
Perhaps the most compelling safety certifications a molecule can receive is the GRAS accreditation from the FDA. GRAS - Generally Regarded As Safe status has been awarded to NR, as well as other forms of Vitamin B3 such as Niacin and Nicotinamide. NMN however has not yet reached this hurdle as of mid 2020.
However, in my opinion, this is inevitable, will arrive soon, and there are currently no reasons other than timing and resourcing as to why this has not yet occurred. NMN supplements are just entering the market en masse (see the above analysis!), and the FDA will be certain to react to this. To be clear, I am not asserting its safety independently, this is the role of the FDA. What I am saying is that closely related molecules have received GRAS status, and the lack of GRAS status for NMN is related to its relative newness in the world of supplementation not due to any known risks.
In summary, NMN is likely to become Generally Recognized as Safe (GRAS), and the other members of the Nicotinamide family (NR, Niacin) have GRAS status. We presently have no reasons to doubt it is a safe molecule to ingest.
NMN Supplementation Risks
However, GRAS status doesn’t ensure it will yield us a positive longevity based outcome. It more or less means it won’t poison us. Safety in this context does not mean there are not risks.
Nicotinamide. Source: Wikipedia
I have spent many tens of hours studying scientific publications available on the topic of Vitamin B3 supplementation and other closely related molecules to NMN (NR, Nicotinamide). What I have found clearly suggests supplementation of Vitamin B3 and its related molecules at high doses. At the most fundamental level, NAD booster supplementation of any form, results in adding significantly higher amounts of B vitamins into the body than it is prepared to metabolise. This is what I would refer to as ‘high doses’ in this context - specifically, consuming 1, 2 or even 3 orders of magnitude greater than the RDA for the vitamin group.
NMN! Source: Wikipedia
Conversely, my research also cemented the claims behind high dose supplementation, as there are a wide array of purported benefits for NMN (limited to mouse studies at the time of writing) and even greater supporting evidence for the benefits of NR (which NMN is converted into prior to entering cells) including early studies in humans. I won’t delve into all of these benefits - if you’re reading this post, you’re likely already sold on the benefits!
In making a judgment call, one is left with a risk management scenario. The possible benefits are significant. However, there are risks associated with high doses of B vitamin intake. To gauge how we make a decision, we turn to the fundamentals of risk management. Understand the motivations for the activity, diagnose the risks of the activity, apply a risk management strategy, and make a decision based on the residual risk.
This means, we next need to understand the risk better, after which we look at the options to managing the risk.
From the abstract:
“However, possible adverse effects and their mechanisms are poorly understood. High-level NAM (Nicotinamide) administration can exert negative effects through multiple routes. For example, NAM by itself inhibits poly(ADP-ribose) polymerases (PARPs), which protect genome integrity. Elevation of the NAD+ pool alters cellular energy metabolism. Meanwhile, high-level NAM alters cellular methyl metabolism and affects methylation of DNA and proteins, leading to changes in cellular transcriptome and proteome. Also, methyl metabolites of NAM, namely methylnicotinamide, are predicted to play roles in certain diseases and conditions.”
NMN Supplementation Primary Risk - Depletion of Methyl Pool
In my review, the primary risk of NMN supplementation (or NR), is the depletion of the methyl group ‘pool’ on which many aspects of your metabolism interact and modulating your DNA expression depend.
A recent study in the journal Biomolecules shares the work of South Korean duo Eun Seong Hwang & Seon Beom Song, who approach this topic from the same place that we opened this blog post - Vitamin B supplementation is growing dramatically in all forms, what are the possible consequences?
Of the many possible negative effects of NMN supplementation, only one of these has been determined to be highly probable. In fact, based on the fundamentals of organic chemistry, it is nearly certain to occur.
Taking high doses of Vitamin B3 (NAM, NMN or NR) will increase the demand on your available methyl pool. This means there are reduced methyl groups available for the methylation of DNA (which, for example, operates in the epigenetic expression of DNA via histones). This could have the deleterious effect of altering your patterns of gene expression and thereby impacting the supply of proteins your cells need to encode for important processes such as cellular repair or replication.
I have adapted the below image from the Biomolecules paper in order to add a bit of clarifying sign-posting on the diagram. From left to right, we have the flow of potential consequences of elevated NAM intake. At far left, the methylation cycle is represented, and at the nexus of it and the NAM cycle, we can see the methylation of NAM (to metNAM) occur. This is what will need to occur in high doses of Vitamin B (NR, NMN or any other form of NAM).
NMN Supplementation Risk Management
Having understood the risk, analysis reveals a critical system (DNA expression, protein encoding) depends on the methyl groups which high doses of Vitamin B are likely to deplete.
So now the question is, can we employ a risk management strategy to minimise this risk?
I believe the answer is yes. Thankfully, it is possible to replenish the cellular methyl pool exogenously via supplementation. Allow me to explain a bit further.
At left in the above image, is an input to the methylation cycle via betaine. Betaine is a metabolite of choline (note how the methylation cycle flows from betaine to choline) and is one of the most important methyl ‘donors’ (another being folate). Betaine can also be called ‘Trimethylglycine’ (TMG). More broadly betaine actually refers to a class of molecules, but in the context of metabolism TMG and betaine are used interchangeably.
TMG is our risk management strategy when it comes to high dose NAM supplementation (including NR and NMN). This molecule is formed of an amino acid (glycine) that has three methyl groups attached to it. It is these three methyl groups that provide the extra inputs we need to support our ramped up methylation cycle when supplementing with NAM. It is possible that different forms of methyl groups, not provided by TMG, could also be required. This will be the subject of future research and updates to featured on the Longevity Blog.
nmn and nr Supplementation gets the green light
Based on the deep dive of research I have been completing on the topics of NAD+ boosters and epigenetics + biological age, I believe NMN supplementation to be risk-appropriate and a potentially effective tool in my longevity supplement stack.
I will soon be embarking upon my own NMN self-experimentation, and as I do so, I will be supplementing with Tri-methyl glycine (TMG) on a 1:1 basis with my NMN intake. In my view, the supplementation of TMG provides self-experimenters with an appropriate risk management strategy for long-term (i.e. more than 1-2 months) NMN (or NR) supplementation.
Need NMN?
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Snag yourself some TMG!
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Four tools for managing cardiovascular disease risk
Cardiovascular Disease kills But longevity technologies help manage risk
In this post, we present you with four immediately actionable ways to ASSESS your risk
If you’re like us — you’re excited about the imminent increases to our healthspan that longevity technologies will soon offer us. However, if you want to stick around long enough to take advantage of all of the soon-to-be available lifespan and healthspan boosting technologies, you need to make sure you don’t die in the process!
But how will you die? Probability states it will be one of the four deadly killers
Atherosclerotic coronary heart disease is the single leading cause of death of men and women in the United States [Source: Medscape]
Ever since science effectively cured infectious disease through antibiotics, vaccinations and the like, there has been a distinct shift in what kills humans to the four deadly killers, which are considered ‘age related diseases’.
These are — cardiovascular disease, neurodegenerative disease, metabolic disease and cancer. If you manage to escape the most likely causes of death as a young person, which are largely accidental death (mostly car accidents), homicide or mental illness related (suicide) — then it is most likely that one of those four deadly killers will end your life.
But here’s the good news — there’s a growing body of immediately actionable longevity technologies that you can engage with to offset your risk of dying of these diseases.
In a series of posts on the topic, we’ll cover a few key resources at your disposal for managing your risk for each of these four categories.
First-up, cardiovascular disease.
Deadly Killer #1 — Cardiovascular disease
Heart attack, stroke, thrombosis, heart failure — the chances are overwhelming that you have lost someone important to you in your life to one of these causes.
It is often seemingly sudden, but in most cases, the acute cause of death by cardiovascular disease has been brewing for a very long time — decades even.
From A to D, the progression of atherosclerosis. At A: healthy aorta with no disease. D: an abundance of plaques and ulcerations.
The term ‘cardiovascular’ encompasses disease of both the heart and blood vessels, which is driven by the build up and eventual displacement of plaque that accumulated in the arterial wall in a process called ‘atherosclerosis’.
It’s not our role to explain all of the mechanisms of this disease.
Instead, we’ll focus on four actionable tools you can work with your doctor to obtain access to, which will help you assess your risk profile and detect any elevated risk of an acute event (e.g. heart attack, stroke) at an early, treatable stage:
1. Action 1 - Test your ApoB (“A-PO-B”)
Stop using your LDL-C as your only risk assessment tool (The “LDL” value too commonly called the “bad” cholesterol), and add tracking of your ApoB.
ApoB is a particular type of molecule attached to the types of lipoproteins carried by your LDL (and VLDL) that are the most likely to enter the arterial wall and lead to plaque formation.
You need to know *how many* of these atherogenic particles you have present in a given volume of you blood — this drives your risk.
Your ApoB value is influenced by diet and lifestyle and can be controlled with pharmaceutical intervention and possibly through certain forms of supplementation.
Learn more about ApoB at Healthline.
Self-order your own Apo-B test (+other cardiovascular markers)!
No doctor required!
HealthLabs.com (USA) - Single Test
UltaWellness (USA) - Panel
I-Screen (Australia) - Panel
2. Action 2 - Do you have elevated Lpa (”L-P-little-A”)?
Lpa is another cardiovascular disease bad guy that may be in your bloodstream.
Lipoprotein-a is a particle which carries cholesterol, fats and proteins and is made by your body, and how much of it you make is inherited.
Elevated levels of Lpa increase your risk of a heart attack or stroke as they are known to cause atherosclerosis.
You certainly need to know if you carry the genetic risk factor, and the earlier the better (i.e. get this test done as early as possible)!
Levels of Lpa don’t change much over one’s lifetime, so testing it once is enough in most cases!
Know your Lpa status, and better know your risk, and whether or not you should modify your diet, lifestyle and treatment options.
Learn more about Lpa from the lipoprotein-a foundation
Self-order your own Lp(a) Test
No doctor required!
HealthLabs (USA) - single test
UltaWellness (USA) - Panel (includes ApoB)
i-Screen (Australia) - Panel (includes ApoB)
3. Know your Coronary Artery Calcium scan score
Coronary artery calcium (CAC) scans are created by using computed tomography (CT) scans, which are a type of X-ray scan, to detect the presence and quantity of coronary artery calcification (the warning signs of atherosclerosis).
A CAC test reveals both the location and quantity of calcium located in three of the main coronary arteries. The scan provides a score which represents your risk.
The lower the better! This score will change over time, and is known to increase with age, so it is important to record it regularly (in a manner that balances the downsides of the X-ray radiation — ask your doctor what’s best for you).
Atherosclerosis is a disease of ageing, and that means your risk is increasing over time. If you are aged 50 or above and have never had one — work with your doctor to get one performed.
Read more about CAC scores in our interview with Health Nucleus Medical Director Keegan Duchicela.
4. Track your inflammation with C-Reactive Protein (CRP)
At its roots, atherosclerosis is known to be intimately connected with inflammation.
In fact, it is often damage to the arterial wall that attracts the formation of plaque in the first place.
This damage occurs over time, and is known to be increasingly likely with high blood pressure and high blood glucose levels.
CRP is a very common and relatively low cost blood test that can be easily ordered up by your doctor, and should be tested annually at the very least.
High levels of CRP are indicative of increased risk of cardiovascular disease, and once again can be influenced by changes in diet and exercise.
If you have the option, go for the high-sensitivity CRP (hsCRP) test if possible!
Self-order your own hsCRP Test
No doctor required!
HealthLabs (USA) - single test
UltaWellness (USA) - Panel (includes ApoB & Lpa )
i-Screen (Australia) - Panel (includes ApoB & Lpa)
Take Action!
Everything that we have discussed in this post encompasses longevity technologies that are available to you NOW.
Ultimately, it is up to YOU to demand access to these technologies, in one way or another. No one is going to do that for you.
If you are aged 50 or older, the importance of getting each of these tests performed is exponentially more important with each decade of life!
Follow us on Twitter for the latest! @longevity_blog
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FDA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These products are not intended to diagnose, treat, cure or prevent any disease.
Body Composition Data - Tracking Lean Muscle Mass and Fat Over Time
InBody and Styku Body Scan Technology - Is it Actionable?
While we are (im)patiently waiting on the results from my blood tests at NextHealth, let’s take a look at another longevity and wellness datapoint that I was able to collect during my recent visit. In my meeting with my “Health Coach” at NextHealth, we completed two types of body composition scans. The first was an ‘InBody’ scan which uses bioelectrical impedance to estimate:
Total skeletal muscle mass
Total body fat in kilograms
Total body fat percentage
Visceral fat
As well as make estimates of your basal metabolic rate and a few other body composition items.
The second was a a Styku which actually uses an Xbox Kinect and a rotating platform to create a full 3D scan of your body.
A key question that I have for these types of body scans and body composition data overall is - “Is this information actionable/valuable?”. In this post, I’ll aim to answer that question from my perspective.
Let’s dive in and take a look at some results!
Comparing my InBody Scan across 18 months
The biggest value in body composition data lies in tracking how it changes over time. On shorter timescales of months to a year, you are able to track how your diet and/or exercise routines are affecting your lean mass, fat mass and/or visceral fat values. Over longer timescales, on the order of several years, you may even be able to track the impacts of aging on your body composition (e.g. the loss of lean muscle mass as the years stack up - yikes!).
I did my first InBody composition scan at the Health Nucleus in May of 2018. At the time, I was about 11 months into a year-long experiment eating a (very clean, whole foods based) ketogenic diet. I was doing an above average amount of physical activity (12k steps/day), but was not ‘working out’ or completing any cardio exercise.
However, that has all changed significantly. As I recently wrote, one of the key outcomes from my visit to the Health Nucleus was a life-long dedication to cardio fitness! So in the 18 months since my first InBody scan, I had added several days/week of cardio training (mostly running), and some strength training (still working on adding more of this), and I had returned to a whole-foods, carb-based diet (retaining plenty of healthy fats). One additional factor on the diet front has been my experiment over 2019 of water-only fasting for 2-4 days per month.
What did my two InBody Scans show (before & after)?
“As you can see here”, Sirish the health coach pointed out with his pen, helpfully marking up my scan results, “Your body is actually pretty symmetrical from left to right. That’s not actually very common”.
I was immediately pleased. Symmetry was something I had been working on religiously, aiming to correct the imbalances I had in my body from left (weak) to right (strong), particularly in my running stride and strength workouts like push-ups.
“Your lean body mass is 157lbs (71kg), and with a total body weight of 177lbs (80kg), that places you at 10.7% body fat, which is at the low end of the normal range”, he commented. “We will get some further detail on this with the Styku body imaging data next”.
“That’s great mate!”, I responded. “That’s actually about the same number I get on my FitBit scale at home”. It was a solid ‘calibration’ of my in-house data, which is very useful.
In the following images (you can click through using the embedded controls), I have add some call-out annotations to draw attention to some actionable insights from my reports.
Conclusion: The InBody scan can definitely provide you with actionable data. Knowing where you stand with respect to your visceral fat mass alone is hugely valuable for assessing your disease risk For me, it was able to provide evidence that changes in my diet and exercise routine had contributed positively to my lean body mass. It also provided me with evidence that my efforts to increase symmetry in my body were fruitful and worth maintaining.
A Styku Haiku
One spinning platform
I stand upon with arms spread
Where did my hand go?
Styku Body Imaging
“Go ahead and strip down to your underwear and jump on this platform.”, Sirish beckoned, “I will step outside until the scan is completed”.
“Naw, mate. I couldn’t care less if you stick around!”, I explained, as I jumped upon the pedestal and started a slow rotation with my arms spread wide. Hey, it was just another day at NextHealth, where between the Cryo, the Infrared Sauna and Instagram, everyone’s half-naked most of the time anyway 😉!
Nudity jokes aside, the Styku scan provided some damn good data! Superceding the InBody scan with its detail, the Styku scan reported on the individual components of the legs, arms and trunk. Despite the accidental truncation of my left forearm (oops!), I was able to get a fairly comprehensive set of data points regarding my lean muscle mass distribution across the body.
Conclusion: The Styku data was certainly actionable. For example, while I had great symmetry in my thighs from left to right, the Styku was able to detect and measure asymmetry in my left and right calf muscles. I now will be adding some additional hypertrophy exercises to that lagging left calf muscle, and hopefully this will lead to performance gains in my race times!
Detailed Styku Results:
Body scan data is actionable - But blood markers will be even more exciting
Overall, I believe that this type of body scanning data is valuable for folks like me, who are trying to optimise their body and mind, relentlessly (hey that’s what being a biohacker is all about!). It may have additional benefits for folks who are overweight/obese, as it can highlight their elevated risks from carrying high amounts of visceral fat. I plan to continue tracking my results with both the Styku and the InBody tools on a yearly basis (and of course I will share what I learn on this blog!).
Body composition discussions aside, I only have to wait a few more weeks until I get the results from the 15 vials of blood I gave to NextHealth. I’m totally jazzed about this, and can’t wait to share what I learn from detailed analysis of my blood. Be sure to subscribe to the blog below to get notified whenever I add new longevity, healthspan and biohacking focused content!
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RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
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My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
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Exercise and Longevity are Inseparable
Aerobic Exercise is Must Have for Longevity
Nick shares a personal story from his Health Nucleus journey in 2018
“Before I came into work to meet you here today, I got in a 40 minute run along the oceanfront”, Dr. Sanders said “I have made it a priority to get in at least four workouts per week, aiming for five or more.”
I sat and listened attentively, as she reviewed my intake questionnaire - noticing my history of high-ish blood pressures and LDL cholesterol values. Dr. Sanders was in her 40s, blonde and super fit - totally unlike any other doctor I’d met along my health journey. Simply put - she clearly walked the talk.
“I recommend you aim for 30 minutes of vigorous physical activity a few times a week. There is hardly a better preventative medicine in our toolbox than that.” she explained. “It can be hard to make a change, but trust me, it will help you with your blood pressure, blood lipids and insulin sensitivity.”
As I took this instruction in, sitting the Health Nucleus guest room (in my awesome socks), I realized I had a bit of reckoning coming my way - I’d come all this way for the latest in all things ‘proactive healthcare’ (full body MRI, genomic sequencing, full blood tests) only to be told, once again, I needed to get more ‘cardio’ exercise. Ugh.
Gasping, sweating, tiring - I’d never really ‘connected’ with the practice of this genre of fitness. I’d had a long-time love for weightlifting, and had dabbled in amateur sports such as flag football and softball.
I’d even enjoyed the occasional cardio-class after an arm-twist from a friend. But that’s not what she was suggesting - this was an overhaul of my life.
To be honest - it didn’t feel immediately doable.
Want Longevity? Exercise Delivers
As I hopped on my plane flight back to Australia from that amazing visit to San Diego, Dr. Sanders’ instruction really stuck with me.
I’d travelled half-way across the world, driven by my ever-growing interest in the fast moving world of longevity and healthspan, enthusiastic about gathering data and personalised guidance for living my best life.
And while many exciting longevity boosting technologies are indeed on their way quite soon (senolytics, gene therapy, stem cell treatments and more!), Dr. Sanders has made it very clear - you can’t avoid nailing the BASICS, which are tried and true, available here and now.
Exercise and a healthy diet form the foundation of wellness, and will continue to do so for the foreseeable future.
All of my research into the topic of longevity, continued to demonstrate this.
There are many different ‘types’ of exercise out there, many wide-reaching definitions and specific examples. But two aspects of it emerged as particularly important for longevity and healthspan during my research on the topic:
1) Resistance exercise (strength training) to build and maintain lean muscle mass; this fights ‘sarcopenia’, which is the loss of muscle mass with age
and
2) Aerobic (i.e. ‘Cardio’) exercise (i.e. training for your cardiovascular system), to strengthen the heart, lungs and circulatory system; this is unequivocally shown to prevent/delay the onset of cardiovascular disease, as well as activate a wide spectrum of protective benefits
Starting a Regular Exercise Habit for Longevity’s Sake!
There are certainly many details that I could share from the past 18 months of my creating a new and enduring habit of regular cardio exercise, and I do hope to share that with you in the future. But I’d like to jump straight to the finish line, literally. Here is a post on my Instagram from last week, after winning a 5k race in Sydney:
I ran that 5K in 20:58! If I had even tried to run 5K back in May 2018, I wouldn’t have been able to complete the race.
So, how did I manage that? What did I do to get in shape?
I’m going to say that’s out of scope for this post, and may decide to share that information with you in the future. That’s not really the point here.
Your healthspan is YOUR responsibility
What is the point is this - one of the major themes of this blog is the power of proactive healthcare.
I’ve provided a bit of a definition on this concept in my opening post, but we’ll need to keep discussing the concept to make it clear what we mean by that term.
Let’s continue that process of elaboration! Proactive healthcare has two major components.
The first and most important part of proactive healthcare is intentionally owning the responsibility we have to our health. Simply put - it is your responsibility to stay healthy.
“The first and most important part of ‘proactive healthcare’ is intentionally owning the responsibility we have to our health. It is our (YOUR) responsibility to stay healthy”
This is an important difference from what has been engendered in our society - that this responsibility is that of your doctor.
Play that game if you want, but it will not necessarily lead you to the long and healthy life you deserve.
Don’t get me wrong - your doctor may be a fundamental part of the journey, but it starts with YOU.
So let me also ‘walk the talk’, as Dr. Sanders does. One of the key outcomes of my visit to the Health Nucleus was this realisation.
That living a long, healthy and happy life is MY responsibility - no one is going to do it for me!
And exercise (Strength and aerobic training) is inseparable from any longevity strategy. We’ll write more on this topic in the future.
Exercise Comes First, Sexy Longevity Technologies Second
It’s only after we’ve begun to take the first part of the proactive healthcare concept seriously, that the second aspect truly becomes powerful.
This second aspect of proactive healthcare is demanding access to the best longevity technologies available.
If you want to be healthy and stay that way for as long as possible, visiting a preventative healthcare facility like the Health Nucleus is a great part of the overall strategy.
But if you decide to join me in this journey of biohacking our way through a long and healthy life, you will not escape making lifestyle changes.
How do I know? Because I had to drag my ‘cardio hating’ lazy ass out of bed and whip my butt into shape like my longevity depends on it! Because it does.
I Took Ownerships and established a ‘cardio’ routine
”That’s absolutely wonderful!” Dr. Sanders said, beaming. “I am just so impressed you were able to make that positive change so quickly and with such determination!”, she remarked.
5K races are my new jam
Staying motivated, staying healthy, staying young!
I’d just dropped the info that I’d actually taken my doctors advice.
We were on a ‘comprehensive return of results’ web video call, after our first ‘preliminary return of results call about 6 weeks earlier.
After the preliminary results call, my Health Nucleus blood results indicated that I was likely a good candidate for improving my results through - you guessed it, cardio exercise.
So, in the spirit of intentionally taking ownership of my health, I said to Dr. Sanders at the end of that first call, “Hey, I’m going to ask you to do something for me.”
“Sure” she volunteered willingly, “What might that be?”
“Please check in on how much cardio exercise I did between now and then!” I asked.
Well, she’d agreed, so I knew my ass was on the line!
That’s just one of the ‘mental hacks’ I used to get myself there. But it is a powerful one.
Is there someone in your life who can provide you with that accountability? If you know you need to ‘get fitter’, then I suggest you start that conversation.
Editorial Note: We have purposefully changed the name of the Health Nucleus Doctor in this story :)
Comprehensive Health Screening: Health Nucleus
Health screening is the future of healthcare
In this short 5-minute video, our founder shares personal thoughts on the future of healthcare, and why it is proactive. The technologies to prevent disease are at your disposal, will you choose to access them?
medical screening in great socks
The Future of Healthcare
includes great socks 🧦
The future of healthcare is based on health screening that is proactive & preventative!
Today, we have all of the medical technology required to detect and treat the most common life-threatening diseases, provided that we can detect them early on.
This includes common killers such as cardiovascular disease (heart-attack, stroke, thrombosis), the chronic illnesses of metabolic disease (diabetes) and, of course, most cancers.
Even health screening and early detection of diseases of the brain (alzheimer's or parkinson’s) can result in extended healthspan, and slow the rate of disease progression (although a cure for these maladies will likely require changing the ageing process itself!)
Health Screening Gets Personal
As our founder shares, health screening is part of a personal motivation for creating Longevity Blog. “In my late 20s, I had three people quite close to me, also in their late 20s, be diagnosed with cancer. In fact, one of them, was my own wife (appendix cancer)!”
“Another had stage III colon cancer. The third, stage IV testicular cancer that nearly took his life.”
In each of these cases, treatments came well after the onset of the disease, which brought on deeper thoughts on the very nature of how we detect and treat these diseases.
Health Screening is how Healthcare catches up to the 21st CenturY
New longevity technologies are being developed and deployed at an increasing pace. Some forward thinkers, including our Founder, observe this trend to be exponential in nature.
This is particularly true for health screening technologies which are directly coupled with progress in computing capabilities (processing power, network communication speeds, memory availability).
However, your personal experience in the healthcare system does not make these changes immediately evident. The healthcare system has made great strides in responsive medicine - treating disease at later stages, after an acute event or advance systems are present.
comprehensive regular health screening is available now
All of the health screening technologies required to detect diseases at an early, highly treatable stage exist NOW (at the time of writing, late 2019).
It is not technological limitations which prevents your access to these technologies. Instead, the limitations are based on 1) knowledge of alternatives, 2) financial means to access them, and 3) your personal demand for access to them.
This foundational post from the Longevity Blog will be followed by all of the information you’ll require to learn about proactive healthcare technologies and how to access them.
It will include our Founder’s personal foray into this technology space, where we’ll use his experience to thoroughly vet and explore these new technologies, to help you decide which to add to your own personalised longevity strategy.
FULL BODY HEALTH SCREENING: the Health Nucleus
Full Body 3D MRI - on the cutting edge of proactive healthcare
As you’ll soon learn, many forward thinking technologists, scientists and medical professionals have already begun to create a healthcare system worthy of the 21st Century.
Where this adventure will start, is at one of the most comprehensive health screening treatment centres in the world: Human Longevity Inc’s Health Nucleus.
Based in San Diego, California, our Founder first visited the Health Nucleus in May 2018. Where he underwent the following:
a wide-reaching blood panel
microbiome sequencing (💩)
What followed on from this visit was a complete transformation in his approach to health and wellness. It’s precisely this type of self-experimenting that helps us create unique content to guide you on your own wellness journey.
Read more about the Health Nucleus in the following posts:
