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The Proof with Simon Hill
Is longevity science overhyped? | Professor Charles Brenner, PhD
Jul 31, 2023
02:26:34
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Quick takeaways
- Longevity genes are not growth hormone genes; animal longevity is polygenic.
- NAD coenzymes play a vital role in repair mechanisms and maintaining cellular function.
- Claims about sirtuins being anti-aging genes are overhyped and lack evidence.
- The information theory of aging suggests the loss of information in DNA contributes to aging.
Deep dives
The Misconception of Longevity Genes
It is misleading to consider growth hormone genes as longevity genes. These genes encode growth factors, and the side effect of their loss is the extended lifespan with no fertility. Animal longevity is polygenic, and there are no strong monogenic longevity genes in humans. Humans, particularly females, can outlive their reproductive capacity due to the importance of mothering and grandmothering in human evolution.
The Role of NAD in Metabolism and Repair
NAD coenzymes, the central catalysts of metabolism, play a crucial role in repair mechanisms and maintaining cellular function. NAD levels can be depleted in response to various insults, affecting repair capacity and contributing to aging. Nicotinamide riboside (NR), an NAD precursor, has shown potential in promoting repair capacity and improving health outcomes in animal and human studies.
Challenging the Sirtuin Theory
The idea that sirtuins are anti-aging genes has been disputed due to flawed and non-reproducible research. Extra copies of sirtuins genes did not extend lifespan in worms and flies in independent studies. Instead, deleting one copy of the fly sirtuin gene extended lifespan in certain conditions. Sirtuins are not candidate longevity genes in animals, and claims of their role in extending lifespan have been overhyped.
Managing Conflicts of Interest
Transparency and integrity are essential in managing conflicts of interest. It is important to avoid making unsubstantiated claims and focus on testable hypotheses. The goal should be exploring the potential benefits of NAD precursors, like NR, in promoting healthy aging and maintaining repair capacity, while recognizing the limitations of current knowledge and the complex nature of longevity.
The Overinterpretation of the Sirtuin Paper and False Claims of Longevity Genes
The podcast episode discusses the overinterpretation of a paper on Sirtuin genes and false claims that they are longevity genes. The episode highlights the initial true findings of the paper regarding the role of SIR2 in controlling ribosomal DNA circles in yeast. However, it criticizes the extrapolation of these findings to suggest fundamental connections to aging in animals and humans, which lacks evidence. The episode also brings up the issue of publishing negative results and the failure to reproduce earlier claims about Sirtuins being anti-aging genes. The discussion explores the scientific controversies and debates related to Sirtuins and their supposed activators, such as resveratrol.
The Information Theory of Aging and Epigenetic Drift
The podcast delves into the information theory of aging, specifically focusing on the interpretation presented by David Sinclair. The theory suggests that aging is caused by the loss of information in DNA and epigenetic processes. It explores the concept of induced pluripotency, where adult cells are triggered to revert back to a pluripotent state, and how this relates to the information theory of aging. The episode critically assesses a recent study by Sinclair's lab that induced premature aging in mice through DNA cutting and attempted rejuvenation using Yamana factors. It questions the experimental design and highlights the lack of functional evidence for rejuvenation, despite improvements in epigenetic age markers.
Key Factors for Healthspan and Slowing Down Aging
The podcast emphasizes the importance of lifestyle factors in promoting healthspan and slowing down the aging process. It encourages physical activity, mental engagement, social interaction, and balanced nutrition. The discussion touches on avoiding metabolic stressors that can disrupt the NAD system, such as UV exposure and excessive alcohol consumption. It briefly mentions the potential benefits of NAD supplementation using nicotinamide riboside (NR) to support metabolism and maintenance of NAD levels. However, it highlights the need for more research on endogenous NR production and its role in physiological processes like lactation and rare diseases.
Episode #272. In the quest for an extended lifespan, has science been led astray? Join me as I sit down with Professor Charles Brenner, a leading global expert in NAD biology, to examine the longevity field's claims and controversies.
From debunking common beliefs to questioning high-profile opinions, Dr Brenner delivers a refreshingly candid perspective on the science of aging. Tune in to explore why he believes there's no “cure” for aging, the limitations of animal studies, and what the future might hold for this complex field.
Specifically, we discuss:
- Intro (00:00)
- Do we have the genes to live beyond 120 years? (3:54)
- The genetics of extreme longevity (14:18)
- Longevity in the animal kingdom (18:26)
- Why do we age, and the realities of extending lifespan (31:22)
- How long can we live? (39:01)
- NAD coenzymes and DNA repair (43:49)
- "Anti-ageing" products (55:17)
- Conflicts of interest and the integrity of scientific claims (1:01:08)
- Discovering nicotinamide riboside (NR) (vitamin B3) (1:03:19)
- Sirtuins as anti-ageing genes (1:09:22)
- A rebuttal to Drs. David Sinclair and Lenny Guarente (1:19:13)
- Seeking consensus on the study of human longevity (1:32:57)
- The information theory of aging (1:43:19)
- Dr. Charles Brenner's theory of ageing (2:00:28)
- How to age better (2:03:30)
- Dr. Brenner on the quality of life (2:09:05)
- NR supplementation (2:10:09)
- Moving beyond Yamanaka factors (2:15:02)
- Outro (2:18:45)
Connect with Dr Charles Brenner on Twitter, and visit his website, https://www.brennerlab.net/, for more.
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Enjoy, friends.
Simon
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Simon Hill, MSc, BSc (Hons)
Creator of theproof.com and host of The Proof with Simon Hill
Author of The Proof is in the Plants
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