Harvard Prof Reveals Age-Reversing Science to Look & Feel Younger w/ David Sinclair
In a Nutshell
Harvard professor David Sinclair reveals epigenetic reprogramming using Yamanaka genes resets cellular age, reversing aging in mice, monkeys, and soon humans via eye injections (Life Biosciences trials January 2025) and AI-designed cheap pills (4 weeks to rejuvenate). Information theory of aging posits epigenome noise, not wear-and-tear, drives decline; sirtuins prioritize DNA repair over maintenance as NAD drops, but reprogramming restores youth, cures diseases like blindness, ALS, and potentially cancer by rebooting self-healing. Longevity escape velocity by 2030s promises doubled lifespans; Sinclair's protocol includes NMN (1g), plant-based diet, exercise, sauna, fisetin, and pulsed rapamycin, urging donations amid funding cuts for trillion-dollar healthspan gains.
These notes were generated by AI and may contain inaccuracies.
Have we reached age reversal technology that truly works? Imagine in 10 years taking a pill for 4 weeks to get younger. Why do we age? The epigenome is the issue because going through sperm, egg, and fertilization resets the epigenome. We've figured out a way to safely reset it without cloning yourself.
We've gone from supplements or exercise to slow aging to truly resetting the body and all cells to be young again. Teenagers today will live into the 22nd century.
Welcome to Moonshots episode on age reversal, focusing on longevity, epigenetic reprogramming, longevity escape velocity, and AI's role. Guest: Dr. David Sinclair, Harvard Medical School professor, author of Lifespan. Discuss near-term developments, support, involvement, benefits. At age 55, David looks 35. We're living in extraordinary times for additional decades of life.
David, welcome. Good to have you back. More focused on health than ever. Muscle mass and exercise remain primary pro-longevity interventions. Eating right, sleep, diet only go so far. Can we turn back the clock?
10 years from now, 2035: state of age reversal technology? Best guess: In Lifespan, predicted wearables, video conferences with doctors, online medicines in 15 years; happened in 3. Sometimes underestimate pace.
Sitting on front row of future. Pace of change is remarkable, head-spinning. 2017: theory to reverse aging. Proved and published in 2020: reverse most aspects of aging by reprogramming cells. Changes everything.
Information theory of aging: Don't just lose information like software corruption; can reset it. From slowing aging to truly resetting body, cells young again by 50, 75, 80, 90%. Do this in lab routinely.
Use genes normally on only in embryos, turn on in adult tissues (mice, monkeys): cure diseases/injuries never cured before, even blindness (published 2020).
Mid-2025: AI advances accelerate. Experiments in a month that would take hundreds of thousands of years: trillions of molecules screened virtually. Alternatives to 2020 gene therapy.
Life Biosciences: Technology into humans January next year. Proven reversal in optic nerve for eye ailments (glaucoma, stroke/Nion). Chose eye for business reasons.
Gene therapies cost $300-400k or up to $2M for rare disease. Producing first batch >$10M. Goal: pennies on the dollar, pill.
Using AI: molecules cost $100 or less for month's course (~$3/day). Work well in mice: reset old animal's physiology in 4 weeks.
Holiday season Hail Mary experiment: oral cocktail Monday/Wednesday/Friday for 4 weeks. Treated mice behaved/physiologically younger; biological age tests confirmed younger.
Plan lifespan study to blow away mouse record if funded.
2035: reversal therapeutic working. Next year: show reversal in human tissue safely (blindness; works amazingly in green monkeys, 95% age reversal in optic nerve, semi-permanent).
On-off system patented: 6-8 weeks on, switch off, eyes stay young, age again then repeat.
Control depth: longer on, younger tissue. Safe so far in monkeys.
Within 10 years: gene therapy body-wide. Life Biosciences moving from viral delivery (AAV since 80s, expensive, off-target, uneven distribution).
Alternatives: lipid nanoparticles (like mRNA vaccines). Legandal (advising): AI finds proteins to direct particles anywhere.
Future: injection of genetic material, become transgenic humans. Turn on 3 youthful Yamanaka genes with doxycycline antibiotic course (safe). For rejuvenation or injury healing.
AI molecules mimic: cheap, swallow, even distribution. In 10 years: pill 4 weeks, get younger.
Longevity escape velocity: Ray Kurzweil predicts by 2030. For every year alive, science extends life >1 year.
Demis Hassabis: end of all disease by 2035. Dario Amodei: doubling human lifespan in 10 years.
Feasible now. 5-10 years ago, far future. Now entering clinic with repeatable age reversal tech (20-100 times).
Possible to double human lifespan. First to live to 150 already born; teenagers today into 22nd century.
For 50s generation (David 56): stay healthy to 90s/100s when tech arrives (exponential pace, AI, digital superintelligence by decade end per Eric Schmidt; cell modeling).
Greenland shark to 500 years, pups at 200; bowhead whale 200; humans to 100 routinely. No evolutionary need beyond ~50 years (war, infection, starvation).
Not wear/tear: about information and entropy. Pristine genome and epigenome (structures reading genome) lost to noise (DNA breaks, chromosome stress, cell stress accelerates aging per 2020 Nature paper).
Body like computer: software corrupts; backup copy resettable.
Time piece on information theory. New proof since Lifespan (2020): papers in Nature, Cell; strong evidence.
Genome: 3.2B letters mom + 3.2B dad; stable, codes ~22,000 genes. Why look different at 20 vs 100?
Epigenetics: which genes on/off. Aging: wrong genes on/off.
Cell: nucleus, chromosomes = epigenome. Unwrap: 6 ft DNA wrapped in proteins. Wrapping fits DNA in cell, controls gene expression (tight = silent/heterochromatin; can't transcribe).
Sirtuins (silent information regulators): bundle DNA (discovered in Lenny Guarente's lab as postdoc; not antioxidants).
Aging: bundles/loops change; cell loses bundling ability; loops open; epigenome changes (genome stable).
Cloning experiments: 23 sequential mouse clones still healthy (mutations wouldn't allow).
Epigenome resets via sperm/egg. Reset safely without cloning: like conception without rebirth.
Skin: collagen genes silenced with age; unsilence in lab (skin project).
Grow human skin/hair organoids: engineer to drive aging forward/backward. Implant in mouse backs (mouse supplies blood): human black hair grows out of mouse back.
Now we can age that hair, make it gray, make it old. And now we test if we can reverse it. And so far it looks good. If you can do that, I think you got another huge winner. I'll never forget at the Abundance Summit, which I've had you speak at a couple times, and you're going to be back in 2026. Eric Schmidt will be our opener. You'll be our closer that year. There was a biotech longevity scientist on stage talking about his technology, how it could cure cancer, increase the health of particular organs and giving this entire list of what it could do and then he says and it can grow hair and the crowd erupts in applause. People do care about skin and hair. We're learning fundamentals about what makes cells old and how do we reverse that and skin is just one.
The original data set that helps the cell remember its original state? Have you found out where that lives? The answer is probably. I'm going to wait to reveal that in detail but I have some very good students working on that right now and we've wrote a review in one of the nature journals about this. If anyone's interested you can go see my ideas but basically what we need for this to be real is there is a memory of youth in every old cell. What is that memory? It's got to be probably something physical. Could be a chemical modification of the DNA. Chemical modifications of the proteins like a methylation or could be methylation. Could be something else. Could be some other type of novel genetic material. Or it could just be proteins that permanently stick to the chromosome and stay there until we need them to reset. People have bumped into this and ignored it because they didn't think it was important. > Your cells remember how to be young. We just need to remind them.
I came to your lab a month ago and met many of them and they are brilliant. They're like my children. Actually, and on some days I love them more than my own children, but yeah, they're very special group and they are working so hard to change the world and make these medicines a reality. We'll talk about the insanity of funding cuts in a little bit and the importance of the work that you're doing.
Anything else you want to add on the information theory? Do you have experiments planned that will just nail this down? When does a theory become accepted gospel? It happens at one funeral at a time. I've been very pleasantly surprised that the theory which is called ITA for short is being well accepted by the community. There's more and more evidence every few weeks about this. What'll really convince people is when we disrupt the observer we call it. This backup copy based on Claude Shannon. I'm a big fan of his. Claude was a scientist at MIT and Bell Labs who figured out the information theory of communication. The reason we have an internet is because of him. The same mathematics and concepts I poached and use for aging. The information theory of aging is all about the preservation of information and having a backup copy which at the time he called it the observer. We still talk in my lab about finding the observer and the observer keeps a backup copy of the original signal and if you lose it by the time it gets to the sender you can go back and retrieve what's missing from the observer. We think the observer has a physical state it's got information there we think we found that information it's novel biology and when we show that breaking that system prevents age reversal from happening then I think that the community will believe us.
We just launched about 18 months ago something called the $101 million Healthspan XP prize. We've had like 625 teams from around the world. This is an X-Prize, one of our largest. We raised $157 million. GSK is a big sponsor as well. Primary two sponsors are Chip Wilson, the founder Lululemon who has a muscular dystrophy called FHD. He put in 36 million. And then a group out of Saudi Arabia called Evolution. Think health and evolution. They put in 40 million. I'm a multi-million dollar donor. We have a lot of incredible people who are supporting this. The goal is can we get the smartest people in the world, including you, working on reversing the loss of cognition, immune, and muscle? I'm amazed the variety of different approaches, and I'm excited that your lab will be participating. We're seeing a huge range from cellular medicines to gene therapies.
Beyond your own work the state of the union for age reversal for longevity is it still an uphill battle in the scientific world in the funding world because it used to be a stigma if you said you're doing age reversal work it was like oh this person's insane. Has that gotten better? Not much. Especially age reversal. There's still the old school in my field that doesn't like the word reversal. But it's somewhat better that at least saying that you work on longevity isn't a stigma. There's a lot more funding outside of academia for this of course but in academia there's less money than ever to study this topic which is surprising given how much potential it has to change medicine. A lot of the funding from this is coming from the crypto community. There's a great alignment between people who believe in crypto is a long-term vision for capital as well and longevity. We've seen Jeff Bezos and Yuri Milner back Altos. We've seen Brian Armstrong back New Limit. We've seen Sam Altman back Retro. If I had that level of capital, I'd be backing like all of them. One or more of these companies could dominate pharmaceuticals in the 21st century. It is a trillion multi-trillion dollar marketplace. I'm on stages and I ask, okay, you're 70 or 80 years old. This is a room of family offices, wealthy individuals, and you're slowly degrading as people do in that last decades. And someone comes up to you and says, "Listen, here is a therapeutic. It will give you an extra 20 healthy years, not 20 healthy years right now, like where you were in your 50s. How much of your wealth would you give for that?" And if they're honest, it would be the vast majority, 80 plus percent. That is tens of trillions of dollars. So I think it's a giant market. I'm hopeful that we'll see a lot more funding coming in from people both philanthropically and investment wise.
The story I like is if you ask someone in their 30s, what would you do to trade with Warren Buffett? No one says they'd trade with him, no matter how much money he has, because he's older. The years you have are worth everything to you. More than money.
What else are you seeing out there that could be a viable age reversal therapeutic? There are a few. I work on epigenetic reprogramming at Life Biosciences and these companies you just mentioned, they're also chasing us. We started a little earlier than they did, but they're trying to catch up. That's a big area and why I'm hopeful that one or more of us is going to succeed. That's for me the most promising. That's why I'm putting my own money into it as well.
Factors from the blood. We know that plasma apheresis exchanging your plasma has some benefits and looks better all the time. Therapeutic plasma exchange. I've done that five times now. I've done it maybe a few times, but I really believe in it because there's a lot of animal data and some human data coming that looks good. What is it about that that's beneficial? We're actually trying to turn that into a pill, but stay tuned for that. It'll be easier than machine for an hour. There's something in our blood that's keeping us old or fresh that comes in that makes us young. There are some factors already companies are working on, but I think there might be a few really good ones that you could take as a drip and rejuvenate. There was a promise of GDF11 years ago. The problem is a lot of these companies get funded with seed capital, but being a biology medical company is expensive and they run out of capital. I think there's something that we haven't found yet that's going to be more rejuvenative. We're screening these proteins in the blood and genes that do epigenetic reprogramming. You could imagine that there's a peptide perhaps or a protein that is circulating in the blood and when it circulates it triggers these genes that give rejuvenation. So we're looking for that.
Stem cells, it's been a bit slow, but we're starting to see a resurgence of stem cell interest and approval. The FDA now approves certain types of stem cell therapy. We've just seen states begin to become much more lenient. Florida is in the process of passing regulation to allow you to do stem cell treatments in state. Utah is there already. Other places, which is great because before this you'd go to Panama or Costa Rica or Antigua to do it, which is fine except you don't have your medical team around you and you're operating ex-US. Fountain Life is going to get into that. We have two centers right now in Naples and Orlando, and we're opening up Miami. And those will all have hopefully the most advanced stem cell therapeutics available, as well as other cellular med like NK cell supplementation. NK cells kill cancer cells. Natural killer cells, your innate immune system, kill cancers. We're always developing cancers and we depend on our immune system to find them and kill them. The same NK cells also hunt down virally infected cells. We're working on a new type of stem cell, a very rare type. There's a stem cell that actually turns into the tissue that it lands in. And that's different than current stem cells. I think that area has promise too.
Senolytic cell killing chemicals somewhat promising. I saw Altos bought a company or is merging with a company that works on that. It's been a little slow, a little bit disappointing with Unity. Unity Biosciences goes public and then their data comes back and they crash and they're slowly eating their way back. It wasn't a complete failure. They just didn't reach the endpoint. There's a lot of variability. But I think they'll keep pushing on and they'll find something. Senescent cells are important. We know from a lot of studies that if you delete these cells, you can improve metabolism and a bunch of other things.
Can you use epigenetic reprogramming to move senescent cells back to normal healthy cells? We have a project in my lab on that and so far it looks like yes we can do both rejuvenation of senescent cells so that they don't cause havoc. They normally cause a lot of inflammation and even cancer. We can stop that with reprogramming but in some cases we can even rejuvenate them so they grow again. Normally they're sitting and they don't grow. There's something called the Hayflick limit right which is about 50 cell replications thereabouts that a cell should replicate 50 times and then have the decency to die and if it doesn't it can become a cancer cell or a senescent cell which is pumping out these inflammatory factors. You can either kill them or you can cure them. It looks like we can cure them, but we're not sure if that's a good thing. We have to figure out if curing a senescent cell will just give us more problems. But at least in tissue culture, it looks like reprogramming does work in that regard.
If you reprogram a cancer cell, what happens? One of my graduate students has been working on this for a few years and we have a lot of evidence that many types of cancers are killed by reprogramming which is interesting if you think about it. You have a cancer cell it's growing you've discovered it at stage three or stage four and it's through different parts of the body. You hit it with an epigenetic reprogramming cocktail and it has the decency to die. It freaks out and realizes it wakes up from its zombie-like state and says, "Oh my goodness, my chromosomes are messed up. I better kill myself." Because one of the ways to become a cancer cell is to ignore its DNA damage. They're filled with DNA damage. When we wake them up, they can. If you wake up a normal cell, it goes back and it gets younger. But if you wake up a cancer cell, it looks like it realizes it should kill itself, and it does.
I want to dive into a couple of your companies that I'm tracking. Life Biosciences and Metro Biotech, two very cool companies. Life Biosciences was founded in 2017-18. They're the ones that have shown in monkeys that you can basically cure blindness and get vision back. The first studies will be in January if all goes well. You've gone originally from mice to monkeys, non-human primates, and it worked as expected in both cases. It worked better than expected actually. So far there's no signs of any reason why we shouldn't go into humans next year. It's going to depend on the FDA, but we're planning to submit what's called an IND shortly. Hopefully by this time next year, we'll know if it's working because the studies are straight into patients. Is it a single injection? It's a single injection. With macular degeneration it's very common to get one injection or more. You don't feel it it's nothing bad. This virus goes into the nerves at the back of the eye and we just turn it on by giving the patient some antibiotic doxy. Doxy is just the trigger that turns on that segment of DNA. We put in those three genes as on inside the virus. We normally have these genes. We're not changing the genome, but by putting these three genes in the virus, we can control them better. And now they're what's called dox-inducible. We could have used any chemical. Doesn't have to be dox. But dox is such a safe easy way. And it's been in research for decades. By this time next year, we should know if it can improve vision in people that have gone blind, either from a stroke in their eye or from glaucoma.
How big will your phase one be? You start with one, then two, then 10. We're just raising money to go into our phase 2 study already. Some of it's bound by confidentiality, but in general that the company has that's phase one for the company. Stage one is proof of concept in the eye. Does it work? Two shots on goal, two diseases. Stage two for the company, which is already underway, is using AI to convert to chemicals, so you have a pill instead. Or an LNP, which is the lipid nanoparticles, so you don't use viruses. Whole body rejuvenation. They're already doing that. Stage three would be going into multiple diseases and eventually whole body rejuvenation.
One of the realizations is for those who develop a disease when you were younger you didn't have the disease. And so if you're able to actually induce some type of age reversal, does that cure the disease? In mice, it's working great. For instance, glaucoma is an age-related disease. You make the eye young again in the animal, the disease goes away. The body can heal itself. That's been really not the approach of medicine as we know it. Medicine is oh, we treat the symptoms of this disease and slow it or cure it, but we don't use the body's own healing properties. Now, we've uncovered the ultimate healing property. We believe that we've uncovered the ability that salamanders have to regrow limbs and fish grow new tails. Similar process and we just turn on these embryonic genes and now we get youth and now the body can heal itself.
Besides vision, what else have we tried? In my lab, we've done Alzheimer's disease, cured. Some muscle diseases cured. ALS, pretty cured. That's important cuz in my partner's family, we have ALS. So that's we're rushing to fix that one. We published it with a collaborator that we could alleviate multiple sclerosis with this as well. So far we have not seen a disease or an injury that could not be effectively treated with this therapy. Now, doesn't mean everything can be cured, but what it's telling me is that diseases that we've been treating really we've just been addressing the symptoms, not the underlying cause. And finally, now we're treating what's really underlying most diseases, which is the aging universal aging process itself. The challenge is today's medical system is built all around just treating the symptoms. It's built around keeping you alive and treating what's possible but not curing you.
Whole body rejuvenation again by taking a set of pills. We don't see like one arm get younger than the other arm. We don't see any of that going on. The notion is that if you're going to be able to reverse the aging of a particular system, skin or muscle or hepatic that it's going to hit all tissues, all organs. That's the ultimate goal and we're already testing in mice how that works. There was another lab, our collaborators out of George Church's lab where we collaborating with George, he's in my department at Harvard. We collaborated initially on building these viruses and they did the experiment that I thought was really interesting, which was just to inject the virus not just into the eye, but inject it into the vein of a mouse. And if we're right, the mice should live longer. And even though this was a hail mary experiment, not optimized, those old mice that they treated lived another 109% longer.
We talk about mice. Lab mice are experimented on everything. A typical lab mouse lives 24 months, 36 months. 20-28 months. Why aren't we seeing mice that are living not two years but 10 years at this point? Because we were taking the wrong approach. What happened to the field unfortunately. In June of 1982, Richard Weindruch and Roy Walford at UCLA showed that life extension of 30 to 40% was possible through calorie restriction to get a mouse to what is currently the record of 53 months. You just have to starve the mouse and you can almost double its lifespan, which I don't think anybody here wants to do. It'll certainly make life feel longer. But those guys showed early on that you can extend the lifespan through diet, but it's not pleasant.
Now we're seeing combination drugs. There was one published last week that combination of two anti-cancer drugs could extend lifespan of mice 30%. So we're approaching the same levels of extension as we saw with those early studies, but ultimately we want to make mice live 10 times longer. Our field has made lower organisms live 10 times longer. What is it about mammals that's harder? I think we were just taking the wrong approach. We were saying, "Oh, let's try this molecule that turns on this longevity pathway or that longevity pathway." Most of these longevity pathways that we worked on starting in the 2000s with molecules to tweak them, we were just slowing aging. We weren't reversing aging. I think with this new age reversal approach and these technologies, the gene therapy and these new cocktails that we have in my lab, we have a much better chance of being able to repeatedly reverse aging and get them to maybe 5 years.
I'm excited about this cuz remember over the holiday break, within 4 weeks, we made them basically young mice again. We want to try this over the lifespan and we've got a good chance. When might you run that experiment? As soon as we have the money to do that.
I do want to hit on a basic idea that I want people to understand which is the idea of these seven sirtuin genes or these proteins and the battle between DNA repair and epigenetic drift. What we have are these seven sirtuins that are conserved across almost all life. Even bacteria. And as they have two functions in the cell, one is to repair DNA damage and one is to make sure that the right genes are on and the
Genes turn off as we age due to accumulating DNA damage. Sirtuins switch between DNA repair and combating epigenetic drift. Internal NAD levels drop by 50% with age. NAD powers sirtuins as the cell's energy currency. With less energy, sirtuins prioritize DNA repair over epigenome maintenance, leading to aging.
Even without NAD decline, distracting sirtuins from gene silencing accelerates aging. In a 2023 Cell paper, researchers created iCE mice (inducible changes to the epigenome mice) with non-mutagenic cuts that distracted sirtuins from chromosomes. After 3 weeks, mice aged 50% faster: tissues, physiology, and DNA methylation clocks showed advanced age.
Researchers reversed iCE mice tissues as an experiment.
AI is central to research; experiments consult AI agents. Two key areas:
- Dash AI: Algorithm visualizes old vs. young cells under microscope, determining age in nanoseconds. Screens genes/molecules for aging reversal by measuring relevant changes (e.g., cells from 20-year-olds to 93-year-olds shift to appearing 20).
- Enables rapid chemical screening with robotics.
Four main enzymes control the epigenome: inhibit three, activate one to reverse aging. Cocktails target these; published six, now down to three. Goal: single safe molecule hitting all four.
AI enables virtual screening of all known molecules against four targets in months. Uses AlphaFold/Deis structures for precise docking (previously manual, days per molecule; now trillions instantly). Selected 100 top candidates (synthetic/natural), ordered like Amazon, now AI-assisted screening.
Massive science funding cuts hit lab hard; 100% government grants terminated, majority of lab funding. Harvard targeted over anti-Semitism claims, affecting innocent students. Delays science, risks lives, ends careers (e.g., colleague retiring to write book).
David fighting on. Extending healthy lifespan by 1 year saves US $86 trillion (Harvard/London School of Business/Oxford study); $366-367 trillion for 10 years via productivity, reduced nursing home/healthcare costs.
David's father (nearly 86) acts/moves/thinks like in his 40s: travels, drives at night without glasses, supervises clinical trials, cares for nephew. Plant-based diet/program contributes. Population like him generates economic value; people delay retirement if healthy/energetic.
Japan example: burden on middle generation caring for sick elders and young.
Lab lost millions in funding, including early-stage grants like Kelly Rich's career grant on ALS (reprogramming treats neuromuscular disorders in mice; close to pill via AI/natural molecules for Serena's mom).
Donate to lab via link (tax-deductible, $50-$1,000). Few million vs. trillions upside/lives saved. Choose thriving future.
Looks great; team found NAD.com list (link in notes).
Basics:
- Sauna, exercise (weightlifting for men, Pilates for women + weights), eating.
- 90-95% plant-based (Serena, nutritionist/chef/longevity expert, changed diet 4 years ago). Stopped much meat; feels better, eats more, mind clearer. Gave up alcohol except celebrations (sensitive: sleepy, weight gain).
- Adversity mode vs. abundance: ≤2 meals/day (often 1), late lunch/breakfast skip. Plants signal adversity via polyphenols.
GLP-1s: Good evidence for longevity if overweight; judicious use (not chronic: muscle loss, kidney/pancreas issues, blindness risk e.g., non-arteritic ischemic optic neuropathy rates doubled/tripled). Tried personally: blood work improved. Use with doctor; pair with workouts to preserve muscle (fasting/GLP-1s cause loss). Oral versions emerging; future longevity role.
Supplements/Meds: Takes ~80/day; advises on longevity.
NMN:
- Not endorsing companies (lawyers stop unauthorized use; no sales).
- Lifespan book made NMN/NAD billion-dollar industry.
- Tests NMN in mice: extends lifespan (mostly females), improves frailty/health. Finds contaminants like endotoxin (inflammatory).
- Invested $30M in human trials (MetroBiotech's crystallized NMN for conditions; assures purity like GSK fish oil drug).
- Not responsible for FDA supplement status; opposed MetroBiotech's FDA push (protects $30M investment). Gray zone now; NMN available.
- Half of supplements mislabeled/degrade (non-crystalline). Goal: raise intracellular NAD+ for sirtuins.
- NMN crosses membrane, converts to NAD (debate: gut transporter per Shin-ichi Shinzani/Washington University; some say breaks to NR first).
Nicotinamide riboside (NR) is used to make NMN in the cell. Some advocate taking NR, others NMN, and some do NAD IVs. NAD IVs likely raise intracellular NAD because it gets broken down and reabsorbed, but evidence is anecdotal. Oral NMN studies (David Sinclair as middle author) in small groups show improvements in blood pressure, cholesterol, lipids, strength, and endurance, promising compared to mouse results. Metro Biotech has five clinical trials on NMN for Alzheimer's, kidney function (details on website), with hopes one succeeds. New molecule MB-725 (successor to MB-626, named after Sinclair's birthday) honors colleague Anthony Sev into who passed during COVID; hopes it reaches market as his legacy.
70% of heart attacks have no precedent (no pain, no shortness of breath); half of victims never wake up. Cancer often undetected until stage 3 or 4. Fountain Life, founded by Tony Robbins, Bill Ackman, Bob Hariri, offers one-stop early detection and therapeutics for extra healthspan via full-body scans. Visit fountainlife.com/peter.
Fisetin: Discovered as longevity molecule before senolytic; activates sirtuins like resveratrol (low doses) and kills senescent cells (high doses). NAD as gas/petrol for sirtuin enzyme; polyphenols like fisetin/resveratrol as accelerator pedal.
Lipoic acid: Sinclair did PhD on it; started taking 15 years ago after Denham Harman (free radical theory originator, worked until 92) recommended it. Free radical theory largely disproven; antioxidants don't extend animal lifespan much, but DNA damage from free radicals accelerates aging indirectly.
Eltorine: Recent Science paper by Raphael de Cabo shows levels don't decline in humans, monkeys, or mice; less promising for lifespan extension, but won't hurt.
NMN dosing: Sinclair takes 1g; studies show 1g doubles NAD, 2g triples it; both safe short-term, no benefit >2g (body pees it out).
Resveratrol, spermidine, vitamin D, vitamin K, low-dose aspirin (81mg baby aspirin with coated to reduce stomach risk): Sinclair takes all. Doctors oppose aspirin due to bleeding risk vs. clot prevention; personalized based on risk (e.g., high Lp(a) like Sinclair/Peter). Excited for new Lp(a) drug in phase 3, out in ~12 months.
Trimethylglycine: Neither takes; no evidence NMN/NAD boosters deplete methyl groups.
Metformin: Both switched to berberine (easier on stomach). Metformin claim of blunting muscle growth misrepresented (only 5% effect, y-axis exaggerated).
Huge claims as longevity drug, but Sinclair less excited: Works in inbred animals/dogs, but human epigenetic age study (6 months ago) showed no effect (vs. caloric restriction, AKG, metformin positive). Risks immune downregulation. Takes pulsed 4x/year, monitors immune cells/cytokines/inflammation. Avoid chronic downregulation: Need active immunity vs. cancer/viruses (e.g., CMV, herpes); ~1000 endemic viruses via deep sequencing cause immunoexhaustion, leaving innate system vulnerable to cancer; CMV linked to autoimmune like multiple sclerosis.
Hormone therapy anti-aging per literature; ways to delay/reverse menopause. Needs vary (e.g., iron, protein monthly). Jennifer Garrison (Buck Institute, X-Prize visioning winner for Double X Prize ovarian longevity). Lab PhD Maria uses age reversal for women's fertility, menstrual fluid as biological clock/diagnostic.
Sinclair uses Healing Sauna (deep infrared, compact ~table size, zips around body, head out; 30min sweat while emailing/meditating). Activates heat shock proteins, toxin removal; science irrefutable.
Fasting/caloric restriction effective if done right: Educated, with vitamins/minerals/protein, regular blood tests (risky otherwise). Align with circadian rhythms, right foods (unhealthy vegan shortens life, healthy extends). Sugar is poison; modern intake 10x higher than 200 years ago. Fountain Life data (200GB: full-body MRI, brain vessel, coronary CT for soft plaque, lung CT, DEXA, 140 blood biomarkers, metabolomics, microbiome, retinal/skin scans): HbA1c highest heart disease correlate (over Lp(a), trigs, LDL, HDL). Control via diet/exercise, acarbose, SGLT2s, metformin/berberine, GLP-1s. New centers: LA Q1 2026, Houston 2025, NY/Orlando/Naples/Miami.
Breakthroughs universal (China works in Chicago, etc.). Longevity clusters: Asia (Singapore), Middle East (Saudi Arabia, UAE, Qatar); West lags (US, bits in UK/Australia). Hope for trillions like AI investment. Aging reversal uplifts societies; needed in South Korea, Japan, China, Italy, Western Europe (population decline). China ~10+ years behind US but gaining via US science cuts.
AI big role in lab since ~3 years ago; daily use. 2 months work = prior thousands of years. Outpaces 5-year predictions; new book Lifespan Survival (2026) updates.
Epigenetic reprogramming for ovarian aging/fertility: Lab (Maria) pursuing; reversed infertility in 16-month-old mice (infertile 6mo prior) via NMN/epigenetics. Only ~5-6 species menopause (3 whale species, humans); sister's menopause age predicts male longevity.
We're very close to making partial cellular reprogramming safe and scalable for human use, with first humans tested by this time next year. Results could confirm efficacy within a year or two, potentially leading to whole body rejuvenation. This feels like science fiction, living in a Star Trek universe with advanced AI.
Life Biosciences human trials for OSK Yamanaka factors start in January.
Next book, Lifespan Survival, releases in 2026. Lifespan was a textbook on why we age and planetary impacts; this is the guidebook for optimizing bodies via evolution, genes, individualized lifestyles, supplements, medicines for maximum longevity, from molecular to societal levels.
Exercise routine: Gym a few times a week or home weights, walk or run on treadmill, especially after 50 to prevent muscle loss—sitting is the new smoking. Tricks: stationary bike during Zoom meetings (appears in space while standing and moving), avoid sitting during the day.
Protein: High intake, mostly plant-based. Gained 10 pounds muscle 18 months ago using creatine (5 grams daily, all upside no downside) and 1 gram protein per pound body weight. Debate on protein amounts; Valter Longo (UCLA) cautions against excess. Dudley Lamming (ex-student) shows branched-chain amino acids (leucine, isoleucine, valine) from meat reduce lifespan; plants have less. Favorite plant protein: lentils.
Single experiment to falsify epigenetic noise theory: Accelerate epigenome aging in ice mice (altering methylation patterns and gene expression). If mice appeared normal and not old, theory disproved. They looked old, supporting the theory (1% chance it worked).
Most useful AI: Identify the observer in cellular rejuvenation by analyzing all world data. Dream: AI figures out cell rejuvenation and publishes the paper. Also, superior drug development: Rank top candidate molecule for humans, simulate via digital twin interactions with body proteins to predict toxicity/safety. Few years away; eventually on your phone to cure diseases.
Non-reproducibility statistic (half of research) exaggerated. Causes: Different cell lines, water supply, handlers, mice behavior—not faking. Some labs thrive on disproving. Easy to fail by changing one variable. Bad science exists (e.g., torine paper single time point, but longitudinal human data supports). Lab standard: Don't publish unless own lab and another reproduce. No papers retracted or conclusions changed.
Need more labs finding new ways to reverse aging beyond three known genes and small molecules. White space opportunity like AI; room for hundreds of successful companies treating/curing most diseases. Competition: Altos. Example: Dr. Alex Zhavoronkov's Insilico Medicine AI/robotic lab—AI proposes experiments, robots run overnight, iterate. Future: Humans supervisory; AI soon surpasses human creativity/imagination, may achieve consciousness. Book recommendation: Brief History of Intelligence by Max Bennett on intelligence evolution starting with language (early LLM stage); few steps to sentience.
Gene therapy initially expensive, but working to make $1 or less per dose. Patents expire; like aspirin. Moderna COVID vaccine $1-2/dose at scale for billions. Few cents/day longevity pill possible for everyone.
Difference: At 22, can fight, get drunk, pull all-nighter, perform high-skill work perfectly. Organs not pristine; epigenome degraded, cells behave like mélange (liver like nerve/skin). Need reboot for perfect function—explains no all-nighters now. Old people just need reboot.
Life meaning: Not enjoying due to finitude worry; every day a joy/gift regardless of 80, 200, 400 years. Historical average lifespan ~30; now 2.5-3x longer, more enjoyable. With AI abundance/cognitive superpowers, stay engaged.
Exercise: Write what you'd do with 20/50 extra healthy years—minds break at 50.
Personal: Continue research, discover new things; solve aging so others handle climate. Father (85-86) loves life, out nightly with younger friends/women, wants another 20 years.
Society: Peg retirement to longevity (Sweden model)—work longer as longevity rises (e.g., +1 year longevity = +1 year work). Revolt likely, but alternative is dying young. With energy/clarity/mobility, want to contribute. Future: AI/Androids/UBI, but health most valuable.
Overpopulation myth: Replacement 2.1 children/family; most below (South Korea 0.7, Japan/Italy/Europe/US low)—economies screwed without longevity/robotics/AI, incentivize families/extend female fertility.
Fertility: Men fertile longer; women drop post-30, career delay unfair (scientists mature at 40, Hollywood misleads). Advice for 20s women: Plan, freeze/fertilize eggs. Protocols delay infertility by delaying aging.
Revert to Star Trek: Explore universe. Uploading: Drosophila connectome mapped; Michael Andreas working on mouse, believes human brain mappable now (destructive). AI cloud confirmation post-upload.
Need positive future visions like Star Trek over Black Mirror/Hollywood dystopias.
Harvard/London Business School/Oxford paper (2021, Nature Aging, Sinclair author): Slowdown increasing life expectancy 1 year worth $38 trillion globally (US-focused willingness-to-pay analysis). Balloons due to positive feedback—more years make people want/pay for more. Reduces healthcare burden (e.g., dementia/ALS like mother-in-law costing tens of thousands/day; healthy at 76 she'd earn/spend). Tell Elon: Prioritize aging over other spending.
Exercise and diet top. Supplements tailored.
Nattokinase: Reverses cardiovascular disease, removes plaque. Chinese study (1,086 people): Up to 95% plaque removal in 1 year at 12 fibrinolytic units (FU)/day minimum (start 6,000 units, consult physician). Sinclair takes for plaque prevention (ultrasound shows no carotid buildup); Peter on 100mg post-COVID/flights for clotting.
OneSkin OS-01 topical peptide reverses skin age (twice daily).
Consult doctors on changes.
One key desire is an AI model that inputs genetics, recent blood work, personal goals like higher cognitive clarity, more muscle, or longevity, prioritizes them, and considers how many pills a day one is willing to take. It would output a prioritized list of recommendations. Currently, different doctors or experts give varying sets of advice, but there is an optimal regimen. The data exists, and building this wouldn't be hard. Doctors often can't keep up with the literature, like not knowing what nattokinase is, but AI can process it efficiently. Work is underway on such a model.
Discussion on sleep: One speaker got a 92 on their Aura ring last night, while the other got a 64, the lowest in a year due to intense preparation and travel. Emphasis on getting sufficient deep sleep as the most important factor. A supplement called Sweet Dreams from Serena (serenaloves.com) induces deep sleep—contains very low-dose melatonin, 5-HTP, and theanine. It has helped overcome severe insomnia, replacing Ambien. Not promoted as endorsement, but shared as what works personally. Disclaimer: Opinions are personal, not affiliated with Harvard Medical School, and not medical advice.
Top longevity gadgets:
- Red light bed (large one like a tanning bed with a lid, e.g., Thor lie-down model).
- Red light panels used mornings.
- Portable red light device placed outside shower for therapy during showers (also a steam shower).
- Red light cap for head/hair growth stimulation, showing results.
At 64, age is stated with pride as a call to action for peak health to reach longevity escape velocity. Feels internally 28-29, looks and moves like 30s-40s. Father at 86 is stronger, fitter, more flexible, with better balance. On recent birthday, did 100 push-ups in a row (previously max 40 in 20s, then 50). Tracks personal metrics like squats, push-ups, planks in longevity guide book. Data from DEXA scans, MRIs matters. Uses Aura ring (brand unspecified). Uses CGM (continuous glucose monitor) about 5 times a year, different brands vary—research what works. Rejects doctors claiming CGMs irresponsible without diabetes; individuals have right to know their genetics, epigenetics, glucose levels—information is power under doctor supervision.
Opposes government prohibiting experimental treatments for terminal patients—right to try under doctor supervision allows informed decisions. Same for euthanasia; if in agony, individuals should have autonomy. Done with physician oversight, not uneducated choices.
Question: How long do you want to live? People have a preconceived number influencing outcomes—mindset powerfully affects lifespan. Better question: When do you want to die? As long as healthy with friends/family, no one wants to die. No one in crowds says yes to dying tomorrow if healthy. > "I don't like the idea of being dead. I think it's pretty boring." Why die if staying healthy, active, and having fun?
David Sinclair's new book Lifespan Survival out in 2026. Podcast The Lifespan with David Sinclair returning this fall—subscribe at davidsinclair.com (A stands for Andrew, after dad).
Support via tax-deductible donations to Harvard Medical School ($50k-$1M levels) through show notes link or Coinbase wallet QR code (stablecoin, Ethereum, Bitcoin). Lab budget $3M/year. Matching $2M or full $3M gets entire personal protocol. Past auction: Lab tour sold for $100k at Steve Aoki event. Friends of Sinclair Lab at $50k level: Email [email protected] for quarterly updates, dinners, investment opportunities, direct access with lab breakthroughs.
Social: Twitter @DavidASinclair, Instagram @DavidSinclairPhD.
Upcoming: Boston end of September; Abundance360.com/longevity for 5-day 5-star longevity trip (capped at 60, with scientists like David Sinclair, George Church, Dean Kamen). Abundance Summit in March. Praise for Sinclair's unique impact and potential longevity legacy.
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