The Biology of Slowing & Reversing Aging | Dr. David Sinclair

A hormone identified as 'pro-aging,' with lower levels associated with longer, healthier lives in studies of animals and certain human populations.

A cellular cleansing system that digests old and misfolded proteins, activated during hunger, with deeper forms kicking in after 2-3 days of fasting.

The idea that mitochondria need a little bit of free radicals to function properly, suggesting that overdosing on antioxidants can be detrimental.

A group of seven longevity genes/proteins that are key to cellular defense against aging, activated by low insulin levels, fasting, and certain supplements.

A hypothesis proposing that periods of cold exposure and hunger, mimicking ancestral conditions, can stimulate the body to burn more energy and improve health.

The system that controls which genes are switched on and off in cells, considered by Dr. Sinclair to be the main driver of aging through information loss (scratches).

A specific sirtuin gene that is activated by low insulin and insulin-like growth factor levels, crucial for longevity.

An artificial sweetener that may have small effects on the body but is not comparable to sugary sodas in terms of detrimental impact.

A biological clock that measures age based on chemical changes (methylation) in DNA, distinct from chronological age.

An enzyme identified by Eric Verdin that 'chews up' NAD+ as people get older, contributing to the decline in NAD+ levels.

Also known as 'zombie cells,' these accumulate with age, cause inflammation, and can contribute to diseases like cancer. Eliminating them or preventing their accumulation can lead to a younger state.

A term coined by David Sinclair and a colleague, referring to how stressed plants make molecules that benefit human health, activating our own defenses against aging.

A cellular pathway that senses protein and amino acid intake; downregulating mTOR during fasting is hugely beneficial for longevity.

An enzyme, similar to superoxide dismutase, that was initially thought to be key to longevity due to its antioxidant properties in the 1990s.

A marker for cardiovascular inflammation, associated with heart disease and predictive of longevity and mortality. High levels indicate a need for dietary changes to reduce inflammation.

A hormone whose expression is controlled by the hypothalamus, found to control longevity in mice, and also triggers the release of fertility-controlling hormones.

A cellular energy sensing pathway, activated by Metformin and Berberine, indicating low energy states that trigger beneficial anti-aging responses.

A brand of zero sugar, grain-free, keto-friendly cereal, mentioned as a nutritious snack option.

A vital small molecule in the body, essential for hundreds of chemical reactions and sirtuin function. Its levels decline with age and obesity.

A naturally sourced, non-glucose increasing sweetener, generally considered safe with no strong evidence of negative effects on the gut microbiome or fasting.

A red wine molecule and sirtuin activator, shown to extend lifespan in mice when given every other day, and needs to be taken with a fatty substance for absorption.

A substance found to extend lifespan in some lower organisms, potentially by interfering with mitochondrial activity. Ingesting it stains the body blue and is considered a dangerous practice.

An amino acid that, when present, down-regulates mTOR, potentially suggesting a pro-aging effect if intake is consistently high, particularly from animal products.

A vitamin from which NR is often made. Taking B3 alone is not as effective at increasing NAD+ levels because the body still needs to find other components like phosphate.

A new type of drug (fortnightly injection) that blocks the release of LDL from the liver, effective for lowering cholesterol and potentially offering pro-longevity benefits.

A substance that some people ingest or put in their eyes, which can stain the skin a silver-purple-brown color with excessive use, considered a 'crazy' practice.

A class of drugs used to lower cholesterol levels, which David Sinclair takes due to family history, despite potential long-term risks.

An enzyme that was initially thought to be key to longevity in the 1990s as an antioxidant, but later research suggested it didn't provide the expected longevity benefits.

A precursor to NAD+, which the body uses to make NAD+ in one step. Taking NMN can double NAD+ levels in the blood and improve endurance in old mice. Recommended dosage is 1 gram daily, taken in the morning.

A substance from tree bark, known as 'the poor man's Metformin,' that boosts energetics like AMPK and Metformin, increases insulin sensitivity, but may not extend worm lifespan.

A mono-unsaturated fatty acid, found in olive oil, that is an activator of sirtuin defenses.

Another precursor to NAD+, which is used to make NMN, then NAD+. In mouse studies, it did not show the same endurance benefits as NMN at equivalent doses.

An artificial sweetener that has been shown to disrupt the gut microbiome in certain cases, but is rarely used anymore.

A molecule found in apples and onions, shown to activate sirtuins and help kill senescent cells.

Colleague with whom David Sinclair published 'The Metabolic Winter Hypothesis,' suggesting that being consistently cold can lead to greater energy expenditure and health benefits.

Scientist who agrees that grapes can cause a significant blood sugar spike.

Professor of genetics at Harvard Medical School, co-director of the Paul F. Glenn Center for the Biology of Aging, and guest on the podcast.

Early 20th-century researcher who first discovered caloric restriction's ability to extend lifespan in rats by 30%.

A researcher in Spain whose lab found that excess iron increases the number of senescent cells in the body.

Former Israeli special forces, author of 'The Warrior Diet,' who advocated for infrequent eating (once per day or every few days) and 'pulsing' the body with nutrients.

The great physicist, known for vocal concerns about the health dangers of x-rays, particularly at the dentist.

Friend who brought a new study on dietary cholesterol to David Sinclair's attention.

Host of the Huberman Lab podcast and professor of neurobiology and ophthalmology at Stanford School of Medicine.

Scientist at the NIH who conducted a study showing that eating within a restricted window (1 hour/day) extended lifespan in mice, regardless of diet composition.

Scientist currently at the Buck Institute, who showed that the enzyme CD38 consumes NAD+ as people age.

Scientist at Albert Einstein College of Medicine who discovered chaperone-mediated autophagy, a 'deep cleanse' mechanism activated after extended fasting.

A friend and colleague of David Sinclair at Washington University in St. Louis, whose research showed NAD+ controls circadian rhythms and NMN improves insulin sensitivity.

Scientist at Albert Einstein College of Medicine whose work showed that inhibiting inflammation in the hypothalamus of a mouse extends lifespan.

Center at Harvard Medical School where Dr. Sinclair serves as co-director, focused on the biology of aging.

Academic institution where David Sinclair is a professor and conducts his research.

Academic institution where Andrew Huberman is a professor and David Sinclair conducts some research.

Medical institution where interesting studies on senescent cells in humans have been conducted.

A personalized nutrition platform that analyzes blood and DNA data to help individuals understand their body and reach health goals. Dr. Sinclair is an early board member and scientific lead.

A sponsor of the Huberman Lab Podcast, known for high-quality, high-precision supplements, and a partner of the Mayo Clinic and major sports teams.

A sponsor of the podcast that makes high-quality, lightweight eyeglasses and sunglasses designed for performance and aesthetic appeal.

A neurodegenerative disease that some associate with long-term statin use.

A fictional character with remarkable healing and recovery powers, used as an analogy for the future of human biology with aging reversal.

Another podcast where David Sinclair has appeared.

A podcast hosted by Dr. David Sinclair, launching January 5th, 2022, focused on the biology of aging and intervention tools.

Website where the biological age test developed in Dr. Sinclair's lab is being rolled out, allowing people to sign up and access their health score.

Podcast where David Sinclair was interviewed, and was humorously noted for drinking a Diet Coke during the interview.

A New York Times bestseller written by Dr. David Sinclair, discussing the biology of aging and potential interventions.

A book written by Ori Hofmekler, advocating for intermittent fasting and pulsing nutrient intake, based on ancient warrior lifestyles.

A prescription drug for type 2 diabetics that mimics low energy, found in epidemiological data to be associated with longer lifespan and protection against age-related diseases. Needs to be timed around exercise.

A long-term, ongoing cardiovascular study that originally identified C-reactive protein (CRP) as being associated with heart disease.