Currently 53 y/o, Dr. David Sinclair certainly does not seem his age. His peers this age may already have gray to white hairs, complain of lower back pain, or been afflicted with health disorders, but not him.
Dr. Sinclair’s longevity stack addresses various mechanisms of aging, including NAD+ levels, blood sugar, and cholesterol levels, oxidative stress, autophagy, senescence, and methylation.
All these drugs/supplements have been linked to aging and longevity, but not all should be used.
Anti-oxidants may fight against aging in conditions with high oxidative stress, but may negatively impact aging during normal physiological conditions.
Consult with your doctor, especially for dosage, prescription drugs, or if you have other underlying conditions.
As a world-renowned scientific leader in the field of aging and longevity, Dr. Sinclair believes living up to 150 years or even longer is possible, and he found ways to delay aging. True to form, his biological or epigenetic age turns out to be much younger than his chronological age. What is his anti-aging secret? Here, we list Dr. Sinclair's longevity and drug stack that was derived from his interviews and books in which he discussed the supplements that he consumes.
1. Nicotinamide mononucleotide (NMN)
Dosage: 1g per day, in the morning.
NMN boosts the production of NAD+, a crucial molecule that fuels a lot of our cellular metabolic reactions needed for survival. NAD+ levels lower as we age and can cause dysfunctions that lead to aging and disease development. Notably, boosting NAD+ levels via NMN intake can delay and even reverse certain aspects of aging.
Dr. Sinclair takes high-dose NMN (1,000mg) to boost his NAD+. It may be a lot, but this dosage may be reasonable since NMN can be destroyed by stomach acid. Some companies even developed special liposomal NMN formulations to protect it and ensure maximal absorption even with lower doses. On the other hand, in a study of older women’s insulin sensitivity, 250 to 500 mg is also adequate.
Dosage: 1g per day, in the morning.
Resveratrol is a compound naturally found in some plants such as grapes, blueberries, and plums. According to Sinclair, resveratrol and NMN complement one another. Resveratrol activates the sirtuins. Sirtuins are anti-aging genes that guard and protect our DNA, but their activities are NAD+-dependent.
The alleged benefits also consist of: encouraging the expression of anti-aging-associated genes, promoting optimal mitochondrial function, and insulin responsiveness, aiding in keeping healthy glucose levels and supporting a healthy inflammatory response.
Dosage: 800 mg, in the evening.
There are pieces of evidence showing that a drug against type 2 diabetes (T2D) called metformin increases lifespan in a variety of animal models, including mammals. People with diabetes under metformin treatment lived longer than those who are not.
However, since metformin is a prescription medication, one must first consult with a doctor. Metformin may also cause diarrhea and gastrointestinal pain temporarily, but this usually passes after a few weeks.
Dr. Sinclair takes metformin to improve his insulin sensitivity and keep a well-regulated blood glucose level. However, research shows that metformin may reduce the benefits of exercise so he skips metformin during the days of his workouts.
4. Vitamin D3
Dosage: ideally 4,000 to 5,000 IU per day.
Vitamin D may increase longevity and lower the risk of several aging-related disorders. Vitamin D deficiency has been linked to heart disease, type 2 diabetes, autoimmune disorders, and Alzheimer's disease.
Vitamin D is essential for the activation of many genes that play important roles in health. While a daily Vitamin D intake of 600 IU for people ages 1 to 70 years and 800 IU for people over 70 years is recommended, long-term daily supplementation of 4,000 to 5,000 IU of vitamin D is also regarded as safe.
5. Vitamin K2
Dosage: ideally 180 to 360 micrograms per day.
In older persons with low vitamin K status, an age-related decline can be observed. Numerous advantages of vitamin K2 include improved skin quality, strengthening of bones, improved mitochondrial function, and better vascular health. Vitamin K2 dose ranging from 180 to 360 mcg per day is standard, while some people with certain conditions like osteoporosis may need even higher.
Dosage: recent status unknown.
Statin, another prescription drug, is well-known for preventing cardiovascular diseases by lowering the levels of LDL (low-density lipoprotein) cholesterol, the well-known bad cholesterol. In effect, people who are at high risk for cardiovascular disease significantly lower the risk of illness with statin treatment.
Not all statins have anti-aging properties and statin intake is associated with adverse effects like myopathy. Simvastatin is one statin that seems to be able to lengthen the lifetime, while other statins do not appear to have this effect. However, up to 50% of patients taking simvastatin (40mg) may develop myopathy.
7. Low-dose aspirin
Dosage: 83 mg per day.
Aspirin is notably used to lower the risk of heart attack, inflammation, and even cancer.
Data from Annals of Oncology released that aspirin is associated with 22-38% fewer cancers in the liver, pancreas, esophagus, stomach, and colon. In colorectal cancer, a 10% risk reduction is observed with 75-100 mg/day and a 35% risk reduction with 325 mg/day.
Meanwhile, a clinical trial with almost 20,000 respondents revealed that intake of low-dose aspirin in healthy elderly (≥65 and above) does not significantly lower the risk of cardiovascular disease or prolong disability-free survival, but even leads to a higher rate of bleeding.
Therefore, since aspirin can damage the stomach and can cause significant bleeding, aspirin use must be prescribed by a doctor.
8. Alpha lipoic acid (ALA)
Dosage: recent status unknown.
ALA is an antioxidant naturally found in spinach, potatoes, broccoli, kidney, and the liver. ALA can reduce LDL and total cholesterol levels, which prevents obesity, and cardiac issues, and alleviates nerve discomfort in diabetic patients.
There has been some excitement about ALA's potential to slow down the aging process, particularly when coupled with acetyl-L-carnitine (ALCAR). However, data on ALA’s effect on aging and longevity is contradicting. Some studies indicate that ALA can prolong lifespan in certain species, while some conclude that it does not impact longevity.
9. Coenzyme Q10 (coQ10)
Dosage: recent status unknown.
Coenzyme Q10 is yet another antioxidant that enhances mitochondrial performance. CoQ10 is thought to extend lifespan since it can directly influence the expression of numerous genes involved in aging and inflammation, and coQ10 supplementation in animal models with coQ10 deficiency proved beneficial as an anti-aging treatment, especially during high oxidative stress conditions.
However, there is also evidence pointing out that like having too little, too much coQ10 in adults may also be harmful. But overall, coQ10 supplementation has contradicting data as an anti-aging regimen. Different studies on animal studies have varying conclusions: it can delay or promote aging, or also may not have an impact on life span at all. Under normal physiological conditions, prolonged coQ10 also induced cognitive impairment in mice.
Dosage: 1 mg per day, in the morning.
Abundant in food sources like blue cheese, soy, shellfish, and mushrooms, spermidine can enhance a variety of longevity and health biomarkers.
Its anti-aging effects are linked to its major ability to induce autophagy, a cellular mechanism to adapt to stress and damage that triggers cellular repair and rejuvenation of certain parts of the cell.
As well-published, spermidine can increase lifespan in a variety of animal models and also delay aging in humans.
11. Quercetin and fisetin
Dosage: 500 mg each, once per day, in the morning.
Quercetin and fisetin belong to a broad family of water-soluble plant chemicals called flavonoids. Flavonoids are not produced by the human body but are found in high amounts in colorful pants (fruits and vegetables of red, green, and blue hues).
Aging causes the accumulation of senescent cells, old cells that already stop multiplying, but don’t die when they should, hence they are dubbed as “zombie cells”.
As a result, it accumulates and can also promote inflammation that accelerates degeneration. As senolytics – a class of compounds that can destroy senescent cells – quercetin and fisetin can effectively eliminate senescent cells, where fisetin appears to be more powerful. In a study published in Aging, fisetin eliminated about 70% of the senescent cells.
12. TMG (trimethyl glycine or betaine)
Dosage: 500 mg to 1,000 mg per day.
TMG, a glycine amino acid with three methyl groups attached to it, is naturally found inside the body. Methyl groups are small molecules composed of 1 carbon and 3 hydrogen atoms (CH3) that are attached to many of our important molecules like the DNA, proteins, and others to ensure or retain appropriate function.
DNA methylation is extremely important. It is correlated with biological age or more precisely, the epigenetic age. The methylation on the DNA controls the activation and deactivation of genes and it should be tightly regulated. Without methyl groups, damage-associated or even cancer-associated genes may become activated, leading to serious health consequences.
As we age, our methyl pools become depleted which may contribute to aging-associated morbidities that people experience. Since TMG is a methyl donor, TMG intake can prevent these dire consequences and promote longevity by preserving or restoring a healthy state.
Meanwhile, the prevalent NAD+ requirement of the body causes the formation of nicotinamide which needs to be removed. The way to do it is via methylation of nicotinamide so that the kidneys can get rid of it. With TMG, methyl levels in the body can be ensured to be enough.
500 mg to 1,000 mg per day is within the standard TMG dosage for supplementation.