The Peter Attia Drive
#35 - Nir Barzilai, M.D.: How to tame aging
Episode guests
Podcast summary created with Snipd AI
Quick takeaways
- Metformin may have anti-aging properties by targeting insulin resistance and glucose metabolism.
- TAME trial aims to prove that targeting aging can prevent age-related diseases in humans.
- Metformin shows benefits in cancer prevention, cardiovascular health, and cognitive enhancement.
- Challenges exist in researching metformin as an anti-aging drug due to dosing and regulatory issues.
- Research on centenarians' genetics reveals potential longevity factors like IGF and FOXO3A gene mutations.
Deep dives
Metformin as a Potential Anti-Aging Drug
Metformin, a drug commonly used to treat diabetes, has shown potential as an anti-aging drug. Studies have demonstrated its ability to extend lifespan and improve healthspan in various animal models. Preliminary data also suggests that metformin may have cancer-preventive properties. Clinical studies have shown its benefits in diabetes prevention, cardiovascular health, and even mild cognitive impairment. Metformin has been associated with lower mortality rates in diabetic patients compared to controls. The drug's effects on aging may be related to its impact on insulin sensitivity and glucose metabolism in various tissues.
Metformin and the Challenge of Clinical Trials
One of the challenges in studying metformin for anti-aging purposes is defining aging as an endpoint in clinical trials. The aim is to prove that targeting aging can prevent multiple age-related diseases altogether. However, regulatory agencies often only consider aging as a biological process and do not recognize it as an indication. Clinical studies, including the TAME (Targeting Aging with Metformin) trial, focus on age-related diseases such as cardiovascular disease, cancer, and Alzheimer's rather than diabetes itself. The TAME trial aims to demonstrate that aging can be targeted and treated as an indication.
The Preliminary Data and Potential Benefits
Extensive preliminary data on metformin's effects indicate that it may have broad-ranging benefits beyond treating diabetes. These include cancer prevention, improved cardiovascular health, and possibly even cognitive enhancement in mild cognitive impairment. Metformin's safety profile makes it an attractive candidate for anti-aging interventions. The drug's effects on aging could be mediated through various mechanisms, such as reducing insulin resistance, modulating glucose metabolism, and altering cellular processes like mTOR signaling. Additional studies and clinical trials are needed to further explore metformin's potential as an anti-aging drug.
Considerations and Challenges for Metformin Research
While metformin shows promise as an anti-aging drug, there are challenges in conducting research and obtaining regulatory approval. Dosing, duration, and patient selection are critical factors that need to be considered in clinical trials. Long-term studies are necessary to fully assess metformin's effects on healthspan and lifespan. Collaborations between researchers, regulatory bodies, and funding agencies are essential to overcome these challenges and advance metformin research as a potential tool to target aging and prevent age-related diseases.
The role of targeted aging in extending healthspan
The podcast discusses the idea of targeting aging as a way to extend healthspan and improve overall longevity. The speaker emphasizes that the ultimate goal is not just to treat individual diseases, but rather to delay the aging process itself and improve health and quality of life. They argue that composite outcomes, which consider overall health and lifespan, are more important than focusing on individual diseases. The speaker also highlights the challenges in funding and study design when researching interventions for aging.
The TAME study and funding challenges
The podcast explores the TAME (Targeting Aging with Metformin) study, which aims to evaluate the effects of metformin on delaying aging and improving healthspan. The speaker discusses the challenges in securing funding for the study and the need for a different conceptual approach to aging. They highlight the importance of demonstrating the proof of principle for targeting aging and the potential future development of more effective drugs and combination therapies.
Insights from centenarians and genetic differences
The podcast delves into the insights gained from studying centenarians and their genetic differences. The speaker explains that certain genetic variations, such as mutations in the grothormon receptor and FOXO3A gene, appear to be linked to longevity. They also discuss the involvement of IGF-1 and how its levels affect aging. The speaker highlights the complexity of genetic factors and their interactions, emphasizing the need for further research to fully understand their impact on aging and longevity.
Exploring the potential of interventions
The podcast explores various interventions and their potential impact on aging. The speaker discusses studies on the effects of exogenous growth hormone and the use of IGF receptor antibodies. The results indicate potential benefits in extending healthspan, but more research is needed to better understand their efficacy and applicability to different populations. The speaker also mentions ongoing studies on other interventions, such as rapamycin, resveratrol, and metformin, suggesting that these interventions may play a role in targeting the aging process and improving overall health and lifespan.
Metformin and its potential impact on aging and cancer
Metformin is a drug that shows promising potential for preventing age-related diseases, including cancer. It has been suggested that metformin may have already saved more lives from cancer than other cancer drugs combined. Clinical studies are still needed to fully understand the safety and efficacy of metformin in aging populations. Nonetheless, metformin has been shown to have various benefits such as weight loss, improved metabolic parameters, and transcript changes related to aging pathways. While more research is needed, metformin holds promise as an affordable and accessible approach to prevent aging and age-related diseases.
The potential of NAD+ precursors and their effect on health and aging
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are precursors of NAD+, a molecule involved in cellular metabolism and energy production. While the mechanism of how orally administered NR and NMN make it into cells is still not fully understood, there have been reported claims regarding their efficacy in improving health and extending lifespan. However, the evidence is mostly based on animal studies, and clinical studies are lacking. The impact of NR and NMN on sleep patterns has been observed anecdotally and in certain studies. More research is needed to understand the effectiveness of NAD+ precursors and their potential role in promoting longevity and preventing age-related diseases.
In this episode, Nir Barzilai, director of the Institute for Aging Research and expert in the genetics of longevity, discusses the evidence that metformin and rapamycin have anti-aging properties and how his TAME study aims to support this hypothesis in humans. Additionally, he describes the role of genetics in lifespan/healthspan and how it might affect important pathways such as IGF and insulin sensitivity.
We discuss:
- Nir’s background and interest in aging and endocrinology [3:30];
- History of metformin, and understanding the mechanism [11:15];
- Attempting to define insulin resistance [21:15];
- Metformin as a possible anti-aging drug [48:45];
- The TAME trial: Targeting Aging with MEtformin [57:45];
- Why Nir believes metformin can slow aging [1:16:30];
- The genetic gift of centenarians [1:28:00];
- IGF/GH and its impact on aging and chronic diseases [1:34:15];
- Genetics/epigenetics of centenarians, gene sequencing, CETP-VV, Lp(a) [1:49:15];
- Should you be taking HGH? [2:05:30];
- NAD and NAD precursors (NR and NMN) [2:30:00];
- Parting thoughts on metformin [2:36:15];
- Possible blind spots in Nir and Peter’s thinking? [2:43:00]; and
- More.
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