How do sirtuins work and why are they important for aging?

Sirtuins are enzymes that control gene expression. They become dysregulated with age, but their activity can be boosted by mimicking calorie restriction or through exercise. They are crucial for regulating lifespan and cellular health.

What is the difference between calorie restriction and intermittent fasting?

While both activate longevity pathways and sirtuins, calorie restriction involves constantly eating less, whereas intermittent fasting involves cycling between periods of eating and fasting. Fasting also shifts metabolism towards fat burning and can induce ketogenesis.

How does NAD+ levels affect aging and bodily functions?

NAD+ levels decrease with age and are essential for sirtuin activity, DNA repair, and overall metabolism. Low NAD+ levels are linked to reduced benefits from exercise, impaired cellular repair, and potentially contribute to aging.

What is the information theory of aging?

This theory suggests that aging is primarily a loss of regulatory information over time, leading to cells losing their identity and not expressing genes correctly. Epigenetic changes are key to this information loss.

Can the aging process be reversed based on epigenetic research?

Research using Yamanaka factors suggests that epigenetic resetting might reverse aging at a cellular level. Studies have shown regeneration in animal models, and scientists are exploring ways to make this process safe for humans.

What are the main NAD+ boosters (NMN and NR) and how do they differ?

NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are precursors that boost NAD+ levels. NMN is directly converted to NAD+ and shows promising results in endurance in mice, while NR requires an additional step.

What is the role of Resveratrol in aging and health?

Resveratrol, found in stressed grapes, activates sirtuins and stress response pathways. It has shown benefits in animal studies for cardiovascular health and may help clear cellular damage by activating autophagy.

How does sleep quality affect aging?

Poor or fragmented sleep significantly impacts health, leading to higher blood glucose levels and reduced insulin sensitivity. Consistent, quality sleep is crucial for regulating bodily functions and mitigating the aging process.

Are NAD+ boosters like NMN and NR safe and effective for humans?

Clinical trials are ongoing, but preliminary research in animals and some human studies suggest potential benefits. NMN shows promise for endurance, and both NMN and NR may support cardiovascular and cognitive health. Long-term safety and optimal dosing are still topics of research.

What are the potential future directions for aging research?

The future involves exploring epigenetic resetting for age reversal. Scientists are working on safer delivery methods, potentially through molecules or pills, to restore cellular youth and treat age-related diseases.

Key Moments

Dr. David Sinclair on Informational Theory of Aging, Nicotinamide Mononucleotide, Resveratrol & More

FoundMyFitness

Science & Technology3 min read73 min video

Nov 6, 2019|642,185 views|14,748|1,103

NAD+nicotinamide riboside nicotinamide mononucleotide resveratrol sirtuins caloric restriction fasting aging epigenetic clock aging clock

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Key Moments

TL;DR

Dr. David Sinclair discusses aging, sirtuins, NAD+, and epigenetic reprogramming for potential age reversal.

Key Insights

Aging is regulated by longevity genes, and lifestyle factors like exercise and fasting can activate them.

Sirtuins are key enzymes involved in aging and lifespan regulation, mimicking calorie restriction benefits.

NAD+ levels decline with age, impairing sirtuin function and DNA repair; boosting NAD+ may offer rejuvenation.

The information theory of aging posits that aging is a loss of information and cellular identity over time.

Epigenetic reprogramming, using Yamanaka factors, shows promise in reversing aging markers and restoring cellular function.

NAD+ precursors like NMN and NR are being investigated for their ability to raise NAD+ levels and their therapeutic potential.

THE DISCOVERY OF LONGEVITY GENES AND SIRTUINS

Dr. David Sinclair's research has identified 'longevity genes' present across species, which are activated by stressors like exercise and fasting. These genes regulate aging, not by adding years, but by extending healthspan. A critical discovery was the role of sirtuin enzymes, which control gene expression and mimic the effects of calorie restriction. When sirtuins are activated, they confer benefits associated with a restricted diet, and their absence negates these benefits, highlighting their central role in the aging process.

NAD+ AS A KEY REGULATOR OF AGING

NAD+ (Nicotinamide Adenine Dinucleotide) is a crucial molecule for metabolism, DNA repair, and sirtuin activity. Its levels naturally decline with age, leading to reduced sirtuin function and impaired cellular maintenance. Sinclair posits that this decline is causal to aging. Lifestyle factors like exercise and fasting can increase NAD+ levels. Boosting NAD+ levels, potentially through supplements like NMN or NR, aims to restore sirtuin activity and trick the body into thinking it's younger, thereby improving cellular repair and function.

THE INFORMATION THEORY OF AGING

Dr. Sinclair proposes the 'information theory of aging,' suggesting that aging is primarily a loss of information and cellular identity. Over time, DNA damage accumulates, distracting sirtuins from their normal regulatory roles. This leads to cells losing their proper gene expression patterns, akin to losing digital information. The goal of interventions like increasing NAD+ is to help sirtuins regain their function, repair DNA damage, and restore the cell's original identity and healthy gene expression patterns.

EPIGENETIC REPROGRAMMING AND AGE REVERSAL

A significant breakthrough discussed is epigenetic reprogramming. Using modified Yamanaka factors, researchers can reset aged cells back to a more youthful state. Early animal studies show that transiently activating these factors can reverse aging markers, improve tissue function, and even extend lifespan without causing tumors. This suggests that aging may not be a one-way street, and cellular rejuvenation is achievable by resetting the epigenome and restoring lost information, though safety and precise control are critical.

NAD+ BOOSTERS: NMN AND NR

Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are precursors to NAD+. While both show promise in raising NAD+ levels in animal studies, NMN appears more effective in some contexts, like increasing endurance. Clinical trials are ongoing to determine optimal human doses and efficacy. Important considerations include the stability of these compounds, as they can degrade, and the potential for more potent, next-generation NAD+ boosters being developed as pharmaceuticals.

REVERSEDAGING RESEARCH AND FUTURE DIRECTIONS

The field is rapidly advancing, with new breakthroughs occurring frequently. Scientists are forming entities to fund human clinical trials, focusing initially on difficult-to-treat conditions like glaucoma. While interventions like fasting and NMN show promise in slowing aging, epigenetic resetting represents a potentially more potent form of age reversal. The ultimate goal is to translate these findings into safe and effective therapies, possibly delivered via pills or infusions, to significantly extend human healthspan and combat age-related diseases.

Mentioned in This Episode

●Supplements

●Software & Apps

●Companies

●Organizations

●Drugs & Medications

●Concepts

●People Referenced

Common Questions

Longevity genes, discovered in organisms like yeast and worms, are genes that regulate the aging process. Activating these genes through methods like exercise or fasting can help repair the body and potentially slow down aging.

Topics

Aging Mechanisms Longevity Genes Epigenetic Clock Information Theory Of Aging

Mentioned in this video

Concepts

Mice

Commonly used animal models in aging research, mentioned extensively throughout the discussion on NMN, Resveratrol, and epigenetic resetting.

PARP

Yeasts

Simple organisms used in early aging research, where longevity genes and the role of sirtuins were first studied.

Nematode worms

Organisms used in aging research, notably in Andy Dillon's lab, where longevity genes controlling lifespan were identified.

Calorie Restriction

A dietary intervention involving reducing food intake by 30-40%, known to activate longevity genes like sirtuins.

Glaucoma

A target disease for the new entity formed by researchers to fund clinical trials in the area of epigenetic resetting.

CRISPR

Organizations

Brigham and Women's Hospital

A hospital where clinical trials for MIB 626 are being conducted.

Harvard Medical School Department of Genetics

David Sinclair's affiliation and the location where he researches the biological mechanisms of aging.

People

Katie Delphia

The medical illustrator for David Sinclair's upcoming book.

Andy Dillon

A scientist whose lab used nematode worms to study the genetics of aging.

Arthur Phillip

Founder of Sydney Colony, mentioned as a historical figure featured in Sinclair's upcoming book.

Tom Kirkwood

A scientist known for the disposable soma hypothesis, which suggests organisms allocate resources between reproduction and bodily maintenance.

Raffaele Rava

A researcher who collaborated with Sinclair on resveratrol studies and conducted primate studies.

Ann Brunie

A Stanford researcher specializing in the epigenomic causes of aging.

Guido Kroemer

A researcher interviewed on the podcast who discusses the signals important for autophagy, including protein acetylation.

Shelley Berger

A researcher at UPenn studying epigenetics and lifespan differences, such as between ants and longer-lived organisms.

Jessica Tyler

Works on the epigenetics of yeast cells, studying protein distribution and cell age.

Supplements

MIB-626

A molecule developed by Metroid Biotech that is currently in clinical trials for safety and efficacy.

Companies

Illumina

A biotech startup where the host worked in the chemistry department during college.

Products

Naked Mole-Rats

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