Who is David Sinclair ?

Dr. David Sinclair is Professor of Genetics at Harvard Medical School and Co-Director of the Paul F. Glenn Center for the Biology of Aging Research. He has gained international recognition for his research on the aging process and methods for reversing it, as well as on health switches that can delay age-related diseases such as Alzheimer's, diabetes, and heart disease. Sinclair was the first to identify the role of NAD+ biosynthesis in regulating lifespan and showed that sirtuins, activated by calorie restriction in mammals, play a key role in longevity. In addition, research in his lab has led to the discovery of small molecules, such as resveratrol, that activate SIRT1, which can mimic the effects of a low-calorie diet and exercise, improving mitochondrial function and increasing resistance to age-related diseases. This literally means that when you take resveratrol, your body starts to feel as if you are undergoing physical exertion and are on a low-calorie diet.

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Sinclair’s team is also investigating how epigenetic changes caused by the shifting of chromatin factors in response to DNA damage may be a major cause of aging, a process that he views as a disease and is developing strategies to reverse these processes in order to rejuvenate cells. His contributions to science have been recognized internationally, highlighted by the awarding of a knighthood. As an Australian, Sinclair has been honored by the Australian honorary system, recognizing his outstanding contributions to science and longevity research. Receiving a knighthood not only highlights the importance of his scientific work, but also the impact it has on improving the lives of people around the world. Dr. Sinclair continues to inspire both the scientific community and the general public. Dr. Sinclair has also received numerous awards for his research, including the Genzyme Outstanding Achievement in Biomedical Science Award and has been named by Time magazine as one of the 100 most influential people in the world. His commitment to research and passion for discovering the secrets of longevity build trust and inspire both the scientific community and the general public.

Sinclair and his team’s research opens new avenues in the field of regenerative medicine and longevity, pointing to the potential of NMN and Resveratrol to slow the aging process and treat age-related diseases. More information about Dr. Sinclair’s research can be found at the Sinclair Lab at Harvard Medical School.

David Sinclair's Supplementation Protocol

Fisetin (500mg)
Dr. David Sinclair has repeatedly touted the potential benefits of senolytics for longevity, compounds that can shut down senescent cells—the dysfunctional cells that accumulate with age and drive several age-related diseases. Yet whenever Sinclair mentions senolytics, he usually mentions both fisetin and quercetin, both of which are powerful anti-inflammatory plant compounds (polyphenols) that have significantly reduced cellular senescence in preclinical studies.

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However, at the 2023 Research Summit, Sinclair did not mention quercetin as part of his supplementation protocol. This came as a surprise to many, but popular metabolism researcher Rimon Lumon, who also runs the Wellness Messiah with Rimon YouTube channel, highlights several possibilities behind Sinclair’s decision in a recent video titled "David Sinclair's 2024 REVISED Supplement protocol | Critical Changes".Analyzing more than 250 studies on quercetin, Lumon suggests that people under 60 should avoid quercetin supplementation, since optimal dosages are likely to be obtained through diet alone. He then points out the potential consequences of over-supplementing with quercetin:

  • Inhibition of sirtuin 6 - a critical longevity-associated protein required for DNA repair, genome stability and metabolic regulation.
  • Inhibition of NRF-2 - a key cellular defense protein that plays a major role in triggering the antioxidant immune response.
  • Reduced glutathione - the most powerful antioxidant in our body, the deficiency of which is associated with aging.

It is unclear whether Sinclair is still cycles quercetin but confirms that he still takes 500 mg of fisetin with yogurt every morning. Some of the notable effects of fisetin in preclinical studies are life extension, alleviating cognitive dysfunctions and brain inflammation, protection against kidney damage and increasing muscle size and strength.

Lipoic acid (300 mg)
Another compound that Sinclair recently revealed as part of his supplement protocol is lipoic acid, a powerful antioxidant that plays a significant role in ensuring our cells have enough energy. Interestingly, David Sinclair conducted his PhD research on this molecule.

He claims that the inspiration to take lipoic acid came from a conversation with relatives of the father of the free radical theory of aging, Dr. Denham Harman, who worked until he was 92 and died at 98. When Sinclair asked Harman's relatives what his secret was to a long and healthy life, they replied that it was lipoic acid.

Sinclair did not disclose the dosage he takes, but the current standard dosage of lipoic acid is 300 mg one to two times daily and is recommended to be taken on an empty stomach.

Fish oil
For the first time in 2023, Sinclair said he’s including fish oil supplements in his anti-aging diet. This is likely a new addition to his protocol, considering he didn’t include fish oil supplements in his bestselling book, “How to Live Long: Why We Age and Do We Really Need to,” in which he first revealed the bulk of his longevity stack.

What makes fish oil supplements so effective are the omega-3 fatty acids, specifically DHA and EPA. These compounds are known for their brain-boosting (nootropic) properties and ability to suppress inflammation, which is key a characteristic feature of aging. Apart from rescuing cognitive decline in preclinical models, recent studies have shown that increased levels of DHA slow down cognitive decline in people with Alzheimer's disease, further underlining their nootropic effects.

While Sinclair didn’t mention a specific fish oil dosage, several longevity experts and physicians, including Dr. Andrew Huberman and Dr. Peter Attia, have mentioned taking 2g of EPA and about 1.5g of DHA.

L-Taurine (AA) - 2 g
Another compound recently added to Sinclair's longevity protocol is L-taurine, an amino acid found abundantly in the body.Apart from extending the lifespan of mice by 10-12% and improved cardiovascular health, taurine's link to longevity is largely attributed to its ability to thwart oxidative stress and improve mitochondrial health, which are most important for healthy aging.

However, on one podcast, Sinclair indicated his confusion about the effects of taurine, as some studies have shown it increases mTOR, a signaling and growth pathway that accelerates aging when overactivated. He stated, “That confuses me… It seems to provide longevity despite mTOR activation.” It’s unclear whether Sinclair will discontinue taurine supplementation in the future, but for now, he takes 2 grams of taurine daily.

NMN - 1g
NMN likely sits at the forefront of Sinclair’s regimen, serving as a precursor to nicotinamide adenine dinucleotide (NAD+), a molecule that plays a fundamental role in cellular energy production, DNA repair, and regulation of aging pathways. Addressing the natural decline in NAD+ levels that is considered a hallmark of aging, supplementing with NMN can restore cellular health and function. As such, NMN has generated excitement in the anti-aging and wellness fields.

Some of the notable effects of NMN in humans and preclinical models include the following:

Resveratrol - 1g
Each morning, Sinclair takes 1 gram of resveratrol with her own plain yogurt. Resveratrol—commonly found in red grapes, wine, dark chocolate, blueberries, peanuts, and cranberries—is a plant polyphenol known to reduce oxidative stress and inhibit “inflammation,” a term coined by scientists because inflammation contributes to the progression of many age-related ailments. What’s more, resveratrol is a potent activator of sirtuins, a family of chaperone proteins that help protect our genetic blueprints (DNA) and improve mitochondrial health.

Despite the fact that David He takes a daily dose of resveratrol himself and encourages others to do the same. He emphasizes, however, that resveratrol is not a miracle drug and should be used in conjunction with a healthy diet, regular exercise and other healthy habits.

Here are some of the notable effects of resveratrol in preclinical studies:

Spermidine - 1-2 mg
Next on Sinclair's longevity list is spermidine, a naturally occurring compound found primarily in wheat germ, mushrooms, green peas, and broccoli.The buzz around spermidine stems from its ability to activate autophagy, the body's process of clearing out damaged cells for repair and rejuvenation.

In addition to increasing the average lifespan of mice and worms, spermidine has protective effect on the heart and beneficial effects on age-related diseases such as cancer and neurodegeneration in some animals. So there's a lot of evidence to suggest it may be beneficial for health and longevity.

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Vitamins D3 (4000 to 5000 IU) and K2 (180-360 mcg)
It’s no wonder that the Sinclair protocol also includes vitamin D3 and vitamin K2, as they play key roles in aging and act as essential nutrients that support overall health. Vitamin D is essential for bone health and immune function, while vitamin K2 contributes to bone density and cardiovascular health. Together, these vitamins work synergistically to promote skeletal strength and cardiovascular resilience, key components in the fight against age-related decline.

Betaine/Trimethylglycine (TMG) - 500 to 1000 mg
The final supplement in Sinclair’s anti-aging regimen is 500 mg/day of TMG, a compound that is naturally produced by the body and is found in red meats (beef, pork, lamb), some fish (salmon, tuna, sardines), and broccoli, among other foods. Sinclair says he takes TMG as a preventative measure for NMN supplementation.

When you supplement with NMN, you have high levels of nicotinamide in your body. When that happens, the nicotinamide is excreted through your kidneys, but it's excreted with methyl groups attached to it. These methyl groups are crucial to various biological processes, such as DNA methylation, a key mechanism that controls which of our genes are turned on and off.

Metformin - 1g
In an interview, Sinclair stated that he takes 1g of metformin for two reasons:

  • "I have a family history of diabetes, and metformin is very effective in treating diabetes and even preventing it. So I do it for medical reasons."
  • "The work of many laboratories has shown that not only animals but tens and thousands of humans in clinical trials have benefited from this drug, which appears to enhance and mimic the benefits of fasting."

Additionally, Sinclair believes metformin may also have an anti-aging effect.

Here are some of the positive effects of metformin use in animal studies:

Low-dose aspirin - 83 mg
Despite mixed evidence regarding cardiovascular benefits, Sinclair continues to include low-dose aspirin (83 mg/day) in its regimen, citing its potential to reduce the risk of cancer.

Rapamycin - dose unknown
The final known longevity drug in the Sinclair Protocol is one that has been on scientists' radar for a while: rapamycin. Originally discovered inside a volcano on Easter Island (Rapa Nui), rapamycin is widely known to mimic the effects of calorie restriction, one of the most tried and tested methods of increasing lifespan in many model organisms.

Scientists believe that rapamycin works by inhibiting mTOR and activating autophagy, both of which are well-established methods for extending lifespan in animals. However, the researchers noted that if rapamycin is taken prematurely, may inhibit growth and development, highlighting the potential trade-off between its benefits for longevity and its influence on developmental processes in early life.

The dose of rapamycin Sinclair was taking is unknown, but in an interview with longevity entrepreneur Dr. Peter Diamadis, Diamadis stated that he took 6 mg of rapamycin once a week.