David Sinclair, the Researcher Who Wants to Cure Aging
If you've ever heard of resveratrol, the anti-aging compound found in small amounts in wine, you can thank David Sinclair, Ph.D., a tenured professor at Harvard Medical School. But Sinclair wants to be remembered for more than that.
Although Sinclair is best known for his research and advocacy of resveratrol in his 30s, he has now moved on to potentially more potent anti-aging compounds and human clinical trials to determine their efficacy.
In the early 90s, shortly before receiving his Ph.D. in molecular genetics at the University of New South Wales in Australia, Sinclair met his mentor Leonard Guarente, an MIT professor who studied genes involved in the regulation of aging.
The meeting convinced Sinclair to apply for a post-doctoral position in Guarente's lab, where Sinclair later discovered that sirtuin 1 (SIRT1) slows aging in yeast. Sirtuins are a type of protein found in many organisms and are thought to protect against epigenetic changes that cause aging.
Later, Sinclair was hired at Harvard Medical School and given a small lab where he collaborated on research that showed the plant polyphenol resveratrol could activate sirtuins.
Theory of xeno-hormesis
To explain why plant compounds seem to affect human aging, Sinclair co-authored a paper in 2003 that coined the term "xeno-hormesis", which can be thought of as interspecies communication of stress signals.
The theory goes that humans have evolved to sense our environment. So when we consume compounds produced by plants in times of stress, our bodies recognize these compounds and get advance warning about poor environmental conditions. This causes our body to activate cellular pathways that make us more resilient and have anti-aging effects.
Sinclair continues to have his own lab at Harvard but has shifted his focus to other, more potent, sirtuin activators such as nicotinamide mononucleotide (NMN). According to Sinclair, human clinical trials are in progress.
Sinclair has co-founded several companies. Arguably the most successful so far has been Sirtris, which was subsequently sold to the pharmaceutical company GlaxoSmithKline (GSK).
At Sirtris, Sinclair had worked to discover 14,000 different SIRT1 activators more potent than resveratrol. GSK apparently still has the molecules, and only a few have been involved in human studies, such as SRT-2104.
Sinclair is also an advisor at InsideTracker, a company that offers consumer blood testing services. Every few months Sinclair receives a comprehensive blood test to check his values and track measures of biological aging.
Books and media
Sinclair has not been shy about making himself and his opinions known on shows such as the Joe Rogan Experience, TED, and a variety of podcasts. He has also published a book about his research and theories.
- Lifespan: Why We Age and Why We Don't Have To – A comprehensive new theory for why we age based on information theory, with the conclusion that “aging is a disease, and that disease is treatable.” Published in 2019. Read our review.
- Joe Rogan Experience #1234
- A Cure for Ageing? – TEDxSydney
- Cracking & Reversing the Aging Clock – Science Unlimited 2019
Sinclair is uncommon among longevity researchers in that he talks openly about his anti-aging routine. He has a specific lifestyle, supplement routine, and blood test regimen that he follows.
- Diet – Sinclair says he eats a "healthy omnivore diet" and as part of this diet avoids pasta and sugar, eats a lot of plants, and avoids meat unless he's worked out. Sinclair fears the mTOR cellular pathway, which is activated by amino acids in protein, may cause aging if activated in excess. In addition, Sinclair does intermittent fasting and often forgets to eat during the day but rather eats later in the night, something he calls a "bad habit".
- Lifestyle – Sinclair tries to take a lot of steps and goes to the gym most weekend with his son. He spends several hours there doing a mix of strength and cardio, sauna, and cold bath. He doesn't smoke and avoids microwaved plastic, UV exposure, and sources of x-rays.
According to his latest book, Sinclair has a specific supplement routine that he has also encouraged his family to use, including his dad, brother, and wife.
- NMN – Takes 1 gram of this NAD+ precursor in the morning. Sinclair has mentioned timing NMN to coincide with the normal circadian rise in NAD+ during the morning. He has also mentioned combining it with trimethylglycine (TMG) for methyl group donation.
- Resveratrol – 1 gram each morning in his homemade yogurt (or other fat) to increase bioavailability.
- Metformin – 1 gram, but Sinclair has mentioned that he has a family history of diabetes, which this drug is prescribed for. There is evidence showing metformin may also prevent cancer, heart disease, and slow aging.
Sinclair believes certain blood values may be associated with longevity and can be used as a metric for biological aging. Since he is an advisor at Inside Tracker he uses their services and gets his values checked every few months.
- Blood glucose – High impact and strong association with aging.
- hsCRP – Medium impact on aging, and shows signs of inflammation.
- Vitamin D – Medium impact on aging, can predict a decline in health and is controllable.
- ALT – Medium impact on aging, and can show signs of liver dysfunction.
- Testosterone (men) / DHEAS (women) – Hormones that have a lower impact on aging compared to the others but are worth watching.
- TNF alpha – Predictor of longevity.