David Sinclair on the Longevity Pill, Age Reversal Timelines, and Updated Protocols | EP #249
In a Nutshell
David Sinclair announces the imminent first human trial of epigenetic reprogramming using OSK genes (a safe Yamanaka subset) to reverse blindness in the eye, with body-wide benefits shown in every tissue—brain, muscle, kidney, immune system, joints—positioning it as a true longevity therapeutic starting tissue-by-tissue before systemic delivery. Small-molecule alternatives, screened via AI, reverse 92-year-old skin cells to 20-year-old states and enter trials soon at ~$200/month scalability. His updated protocols: resveratrol (with fat for absorption), NMN, metformin/berberine for glucose control, nattokinase (8-10k units) for plaque reversal; mostly vegan diet, no daily alcohol, stress reduction via meditation/relationships, 3 cups coffee/tea daily. Age reversal in humans possible by 2026, no biological lifespan limit.
These notes were generated by AI and may contain inaccuracies.
This feels like another Wright brothers moment. Once you can fly, everything changes. We're about to learn whether we can fly. We're days away from the first human epigenetic reprogramming trial using three of the Yamanaka genes, a subset, going into the eye of a patient to cure blindness. Every tissue shows benefits: brain age reversal, improvement in memory, motor neurons for ALS, immune system, muscle, kidney, liver, skin. A true longevity therapeutic works throughout the entire body.
Is there an upper limit to how long humans can live? I'm not saying that, but I am saying that.
David drinks coffee, about three cups a day. Studies show caffeine and decaffeinated coffee are good due to other molecules. Coffee is currently in positive fashion for longevity. It's a good way to start the day. Caffeine is fine. David and Serena drink tea all day until they can't take more caffeine.
Drug candidate from David's lab published in 2020 on the cover of Nature magazine titled "Turning Back Time." Student Wangloo found three genes (OSK, subset of Yamanaka genes) that safely reverse aging without causing cancer or loss of cell identity. Yamanaka genes make stem cells, but full set kills mice in 2 days. OSK going into human eye shortly to cure blindness after success in mice and monkeys. Investors in Life Biosciences excited about reversing blindness.
Didn't choose eye because it works best; David recommended liver instead, next target. Every tissue benefits: brain age reversal, memory improvement in old age and Alzheimer's models, motor neurons for ALS, immune system, muscle, kidney, liver, skin, joints. New paper last week showed regrowth of joint, cartilage, bone. True longevity therapeutic works body-wide.
Starting tissue by tissue due to FDA caution; untested in humans. Life Biosciences approved for clinic. Future: intravenous for whole body using lipid nanoparticles or chemicals. Current therapy uses AAV gene therapies, expensive ($500K-$2M), targeting glaucoma, goal to reduce price.
2017 technology (OSK gene therapy) going into humans imminently; patients recruiting. Since then, developed cheaper small molecules using AI to screen billions, now testing in lab on 92-year-old human skin cells to reverse to 20-year-old. Proof of concept: three-molecule cocktail, some published years ago, entering clinical trial in months via Healthspan X-Prize. Currently expensive at kg scale (hundreds of thousands), but scalable to cheap like metformin. Predicted $200/month. Goal: single molecule, accessible to 8 billion people.
Technology starts expensive for wealthy, becomes affordable. Like Wright brothers: initially elite, then mass access faster than aviation history.
Wave of research ensures it happens in our lifetime, possibly 2026 when we learn age reversal possible in humans. Part of longevity singularity. X-Prize with Jamie Justice accelerated chemical cocktail to humans.
Early work faced pushback and stigma; David persisted.
No law says we have to age. Can live hundreds of years, as in animals; humans up to 122. No biological or physical limit. Reboot system resets cells to young state, not just healthier. Can reboot multiple times; mice died of old age with good eyesight after repeats in eye.
Once you can fly, everything changes. We're about to learn if we can fly. Pretty sure we can.
A year ago on Moonshots podcast, funding cut ($2-3M/year including fellowships) due to White House-Harvard battle; had to let grad students go. Created Friends of Sinclair Lab (FOSL); raised $6M private annual support. Grant system funds predictable science, 10% success rate, retrospective. FOSL funds directly radical experiments.
Now better funded, faster progress; no time wasted on grants. Example: student needed kidney; Brett Blundy funded project immediately.
70 members, limiting growth for community feel; waitlist. Contact Peter, Max, Marissa. Members text David, visit lab, dine with him and Serena, learn discoveries early.
What wrote in Lifespan (page 304) still holds. Don't post publicly due to products misusing his face.
- Resveratrol (from red wine): staple for 15+ years, mixed with olive oil/yogurt/oily/proteinaceous food for absorption (passes through otherwise). Activates sirtuins (longevity enzymes), linked to reprogramming and information theory of aging. New Nature submission data.
- NMN (nicotinamide mononucleotide): don't confuse with M&M's.
Third supplement is a glucose-lowering medicine. Two of choice, cycles between them with Serena. Metformin requires prescription, type 2 diabetes drug, relatively safe, take 1 gram a day. Can cause stomach upset. Natural version is berberine, has clinical data, benefits include lowering blood glucose. Glucose levels are really important—monitor glucose, pasta, carbs, especially processed carbs. At Fountain Life, number one correlate with heart disease is hemoglobin A1C (glucose levels), not HDL, LDL, or Lp(a).
New addition in last couple years: nattokinase, an enzyme. Only thing clearly shown in large trials (thousand plus people) to reverse plaque. Natural enzyme from natto (Japanese breakfast that smells like vomit). Serena likes natto, takes pills instead. Needs at least 8,000–10,000 units based on trials (6,000 didn't work), takes a year, must be consistent. Doing experiment, will ultrasound carotid again to check IMT (intima-media thickness). Avoid dying from stroke or heart attack—get CT scan (radiation accelerates aging) or prefer ultrasound (safe, 20 minutes on neck). Fountain Life offers carotid scan yearly on longevity trip.
Mostly vegan, struggles with good food like Japanese sushi. Serena inspired shift. At gathering for Friends of Sinclair Lab, admitted Serena turned him on with talk of navitoclax and dasatinib as senolytics.
What turned me on with Serena was her talk about navitoclax and dasatinib as a senolytic. Wow, this woman's amazing. Keep talking chemicals, it's turning me on.
Changed view on alcohol—data damning, even one glass a day correlates with smaller brain. Stopped a few months after meeting Serena (she's teetotaler). Few times a year ok to celebrate, but not daily. Used to do cheese and red wine nightly as "Mediterranean diet"; Serena stopped it, biomarkers improved (inflammation way down) within a month.
Benefit of alcohol is social lubricant for relaxation. Challenge is pace of travel, work, stress as countervailing force.
Serena changed life—taught meditation, breathing, chilling. Was hard on self, ruminating, stressing if not number one, lived on edge until meeting her. Now sleeps better, looks/feels better; constant tension accelerates aging (proven). Blood pressure, cholesterol, blood sugar good for longevity. Get a pet, partner. Surround self with loving people, avoid loneliness—it kills. More hugs.
Get a pet, get a partner. Just make sure that you're socially surrounded by people who love you and you are not lonely because loneliness will kill you. More hugs in your life.
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