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 to reverse 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 demonstrated that sirtuins, activated by caloric 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. Literally, this means that by taking Resveratrol, the body begins to feel like it is undergoing exercise and a low-calorie diet.

Sinclair's team is also studying how epigenetic changes caused by shifting chromatin factors in response to DNA damage may be a major cause of aging, a process he treats like a disease, and is developing strategies to reverse these processes to rejuvenate cells. His contributions to science have been recognized internationally, highlighted by his being awarded a knighthood. As an Australian, Sinclair was honored by the Australian honor system, recognizing his outstanding contributions to science and longevity research. Receiving a knighthood not only underscores the importance of his scientific work, but also the impact he is having 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 was named by Time magazine as one of the 100 most influential people in the world. His commitment to research and passion for unlocking the secrets of longevity build confidence and inspire both the scientific community and the general public.

The research by Sinclair and his team breaks new ground in the field of regenerative medicine and longevity, indicating 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 on the Sinclair Lab website at Harvard Medical School.

David Sinclair's supplementation protocol

Fisetin (500mg)
Dr. David Sinclair has repeatedly emphasized the potential benefits of senolytics for longevity, compounds capable of extinguishing aging cells - dysfunctional cells that accumulate with age and drive several age-related diseases. However, whenever Sinclair mentions senolytics, he usually mentions both fisetin and quercetin, both of which are potent anti-inflammatory plant compounds (polyphenols) that have significantly reduced cellular aging in preclinical studies.

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 metabolic 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 the age of 60 should forgo quercetin supplementation, since optimal intake can probably only be achieved through diet. He then points out the potential consequences of excessive quercetin supplementation:

Inhibition of sirtuin-6 - a critical protein associated with longevity, essential 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 potent antioxidant in our body, the deficiency of which is associated with aging.

It is unclear whether Sinclair is still cycling quercetin, but he confirms that he continues to take 500 mg of fisetin with yogurt every morning. Some of the notable effects of fisetin in preclinical studies include prolonging life, alleviating cognitive dysfunction and brain inflammation, protecting 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 potent antioxidant that contributes significantly to providing our cells with sufficient energy. Interestingly, David Sinclair conducted his doctoral 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 the age of 98. When Sinclair asked Harman's relatives what his secret to a long and healthy life was, they replied that it was thanks to lipoic acid.

Sinclair did not disclose the dose he takes, but the current standard dose of lipoic acid is 300 mg one to two times a day, and it is recommended to take it on an empty stomach.

Fish oil
For the first time in 2023, Sinclair said he was including fish oil supplements in his anti-aging diet. This is likely a new addition to his protocol, given that he did not include fish oil supplements in his best-selling book “How to Live Long. Why We Age and Do We Really Need to,” in which he first revealed most of his stack for longevity.

What makes fish oil supplements so effective are the omega-3 fatty acids, particularly DHA and EPA. These compounds are known for their brain-enhancing (nootropic) properties and their ability to suppress inflammation, a key characteristic of aging. In addition to rescuing cognitive decline in preclinical models, recent studies have shown that elevated levels of DHA slow cognitive decline in people with Alzheimer's disease, further highlighting their nootropic effects.

Although Sinclair did not mention a specific dose of fish oil, several longevity experts and physicians, including Dr. Andrew Huberman and Dr. Peter Attia, mentioned that they take 2 grams of EPA and about 1.5 grams 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. In addition to extending the lifespan of mice by 10-12% and improving cardiovascular health, taurine's link to longevity is largely attributed to its ability to thwart oxidative stress and improve mitochondrial health, which are paramount to healthy aging.

However, in a podcast, Sinclair pointed out his confusion about taurine's effects, as some studies have shown that it increases mTOR, a signaling and growth-promoting pathway that accelerates aging when over-activated. He stated: “This confuses me... It seems to provide longevity despite mTOR activation.” It is unclear whether Sinclair will stop taurine supplementation in the future, but for now he is taking 2 grams of taurine daily.

NMN - 1g
NMN likely stands at the forefront of Sinclair's scheme, 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. Referring to the natural decline in NAD+ levels, recognized as a hallmark of aging, NMN supplementation can restore cellular health and function. As such, NMN has generated excitement in the field of anti-aging and wellness.

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

Resveratrol - 1 g
Every morning, Sinclair consumes 1 gram of resveratrol with homemade natural yogurt. Resveratrol - commonly found in red grapes, wine, dark chocolate, berries, peanuts and cranberries - is a plant polyphenol known for reducing oxidative stress and inhibiting “inflammation,” a term coined by scientists due to the fact that inflammation contributes to the progression of many age-related ailments. Moreover, resveratrol is a potent activator of sirtuins, a family of guardian proteins that help protect our genetic blueprints (DNA) and improve mitochondrial health.

Although David himself takes a daily dose of resveratrol and encourages others to do the same. However, he stresses 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:

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

In addition to increasing life expectancy in mice and worms, spermidine has protective effects on the heart and beneficial effects on age-related diseases such as cancer and neurodegeneration in some animals. Thus, there is ample evidence to suggest that it may be beneficial for health and longevity.

Vitamins D3 (4,000 to 5,000 IU) and K2 (180-360 mcg)
Not surprisingly, the Sinclair protocol also includes vitamin D3 and vitamin K2, as they play a key role 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 maintaining 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 weakness.

Betaine / Trimethylglycine (TMG) - 500 to 1,000 mg
The final supplement in Sinclair's anti-aging regimen is 500 mg/day of TMG, a compound naturally produced by the body and found in red meat (beef, pork, lamb), some fish (salmon, tuna, sardines) and broccoli, among others. Sinclair says he takes TMG as a preventative measure for NMN supplementation.

During NMN supplementation, there are high levels of nicotinamide in the body. When this happens, nicotinamide is excreted by the kidneys, but it is excreted with methyl groups attached to it. These methyl groups are crucial for various biological processes, such as DNA methylation, a key mechanism that controls which of our genes are turned on and off.

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

“There was a history of diabetes in my family, and metformin is very effective in treating diabetes and even preventing it. So I do it for disease reasons,” he said.
“The work of many laboratories has shown that not only animals, but tens and thousands of people in clinical trials have benefited from this drug, which seems to enhance and mimic the benefits of fasting.”

In addition, Sinclair believes that metformin may also have an effect on slowing down the aging process.

Here are some of the positive effects of metformin 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 cancer risk.

Rapamycin - dose unknown
The last known longevity drug in Sinclair's protocol is one that has been on scientists' radar for quite some time: 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 for increasing the lifespan of many model organisms.

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

The dose of rapamycin taken by Sinclair is not known, but in an interview he conducted with longevity entrepreneur Dr. Peter Diamadis, Diamadis said he takes 6 mg of rapamycin once a week.