David Sinclair is a professor of genetics at Harvard Medical School. He is most known for his academic work in the field of aging having discovered the role that the Sirtuin 1 protein plays in slowing down aging in yeast.
David Sinclair has also co-founded several biotechnology companies including: Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, and Liberty Biosecurity.
David Sinclair has spent the majority of his life studying the cause of aging and his biohacking mostly revolves around self-experimentation with anti-aging compounds. He believes that aging should be classified as a disease and that future drugs and therapies will be able to significantly extend health lifespans in humans. While he does not describe himself as an immortalist, he believes that there is no optimal lifespan. On Dave Asprey's Bulletproof Radio podcast episode he stated that he expected to live to 100-years-old.
David Sinclair approaches his anti-aging regimen as a scientist and monitors his biomarkers (liver enzymes, see InsideTracker) closely.
David Sinclair's Biohack Stack, Regimen, and Routine
Metformin, 0.5g per day - A diabetes drug that is currently being studied for efficacy in delaying age-related disease in a FDA trial (see TAME). Only taken on days when not exercising.
I've been following David Sinclair ever since I discovered him through Twitter / The Peter Attia Podcast
Sinclair is a professor of genetics at Harvard who has spent nearly 30 years studying aging. The compounds he takes in the hopes of slowing down aging are promising but warrant further investigation. Sinclair has repeatedly stated he does not tell people what to take, instead choosing to simply share what personally takes. He has readily admitted on previous podcasts that he takes a self-experimental approach to anti-aging compounds such as metformin and NMN. It is important to remember to neverblindly follow someone else's regimen or biohacking stack. Any medical treatment should be done under the supervision of a licensed medical professional.
Sinlair's opinions on exercise and diet are probably more informed than the average layperson, but I don't think they are really his field of expertise per se. He has stated that nobody knows what the perfect diet is. However, given his professed desire to live to 100 and "outlive his enemies", his regimens are worth investigating for yourself.
Information Theory of Aging
David Sinclair believes that aging can be traced back to a single fundamental cause: The loss of epigenetic information. Loosely speaking, the epigenome refers to chemical modifications of the genome that do not alter DNA sequence. These modifications regulate gene expression and Sinclair believes that over time noise and loss of this information causes cells to begin to lose their identities, malfunction, and result in aging of an organism.
Epigenome modifications include things like histone alterations and DNA methylation, the latter being the basis for Steve Horvath's epigenetic clock.
Three Levels of Anti-Aging
Sinclair divides anti-aging interventions into three different levels:
Level 1: Reset gene transcription factors through hunger (caloric restriction, intermittent fasting, time restricted eating)
Level 2: Silencing certain (antagonistic pleiotropic?) genes for a long time through exercise, diet, and compounds that activate sirtuins like metformin.
Level 3 "Deep Layer of Aging": Therapies in development today. Targeting epigenetic noise (methylation, histone markers, etc) permanently.
The number one thing David Sinclair recommends
According to Sinclair, the number one thing you can do right now to slow down aging is be hungry more often. Fasting activates gene pathways that tell our cells to hunker down and repair.
NR vs NMN
David Sinclair takes the NAD+ precursor NMN (nicotinamide mononucleotide) over the other popular precursor, NR (nicotinamide riboside), since he has already has a "stash" of NMN. He also believes that NMN is the more chemically stable compound. Otherwise, from an efficacy perspective, he suspects they are roughly the same.
David Sinclair has spoken many times about his 80-year-old father's experimentation with David's anti-aging regimens (Metformin, NMN, Resveratrol). Anecdotally, it appears to be a great success. Sinclair has previously said that if you were to "put a bag" on his father's head, one would think he was 40 instead of 80.
Antagonistic Pleiotropy -- What helps us in young age hurts us in old age
Sinclair believes in the theory of Antagonistic Pleiotropy for aging - that some of the genes that provide fitness in early life become detrimental in aging.