Dr. Nir Barzilai: Can This Drug Slow Aging? The Science Behind Metformin
Feb 7, 2024
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Dr. Nir Barzilai, a leading geroscientist and professor at Albert Einstein College of Medicine, dives into the fascinating world of aging research. He discusses the groundbreaking potential of metformin to not only manage diabetes but also to delay aging. The conversation also touches on insights from centenarians, the impact of genetics on longevity, and the role of the microbiome. Barzilai shares his pioneering work with the TAME trial, aiming to convince the FDA that aging can be treated, transforming our understanding of healthspan and lifespan.
The TAME study aims to show that metformin can prevent age-related diseases and delay aging.
Genetic factors play a role in aging, and targeting specific genes can slow down the aging process.
Peptides, such as humanin, show potential in promoting healthy aging but require further research.
Repurposing drugs, like metformin, for aging-related trials is a promising approach to preventing age-related diseases.
Deep dives
Metformin and the Targeting Aging with Metformin Study (TAME)
The TAME study, targeting aging with metformin, aims to show that metformin can target the biology of aging and prevent age-related diseases. Metformin, a drug developed in 1957 to treat diabetes, has been found to have potential anti-aging effects. Observational studies have shown that individuals taking metformin have lower mortality rates and reduced risk for conditions such as cardiovascular disease, cancer, cognitive decline, and Alzheimer's disease. The TAME study seeks to provide rigorous clinical evidence to support the use of metformin as an anti-aging intervention. Its goal is to show the FDA that targeting the biology of aging and preventing age-related diseases is a viable approach. By demonstrating the potential of metformin to improve various hallmarks of aging, the study could pave the way for metformin to be approved as an anti-aging therapy.
Genetic Factors and Aging
Research on super-agers, individuals who live to be centenarians while maintaining good health, has revealed the importance of genetic factors in aging. Genetic studies have shown that certain genetic variations can slow the aging process and promote longevity. For example, a mutation in the growth hormone receptor gene has been found in a significant proportion of centenarians, and this mutation is associated with improved cognitive function and longer lifespan. Another genetic variation that has been identified in super-agers is a mutation in the CKB and ABI3 genes, which is associated with higher levels of HDL cholesterol, or the 'good cholesterol,' and reduced risk of diseases such as diabetes. These findings highlight the potential for targeting specific genetic factors to slow aging and promote healthy longevity.
Peptides and Aging
Peptides, short chains of amino acids, have gained attention in the field of aging research due to their potential anti-aging effects. One example is humanin, a peptide derived from the mitochondria, which has shown promising results in animal studies. Humanin has been found to improve cognitive function and reduce the risk of diabetes. Other peptides, such as Mots-C and IGF-PP, have also shown potential in promoting healthy aging. However, it is important to approach peptide use with caution, as their effects and safety profiles are not fully understood. Rigorous clinical studies are necessary to assess the efficacy and safety of different peptides before widespread use can be recommended.
Conclusion
In conclusion, the study of metformin, genetic factors, and peptides in relation to aging offers promising insights into potential interventions for promoting healthy aging and extending lifespan. The TAME trial is a significant effort to evaluate metformin as an anti-aging therapy and pave the way for future research on aging interventions. Genetic variations associated with healthy longevity highlight the importance of genetic factors in aging and the potential to target specific genes for intervention. Peptides show promise in promoting healthy aging, but further research is needed to determine their efficacy and safety. As the science of aging continues to advance, it is becoming increasingly clear that a holistic approach, combining lifestyle modifications, genetic insights, and targeted therapies, may hold the key to healthy and extended longevity.
Repurposing Drugs to Target Aging
The podcast discusses the concept of repurposing drugs to target aging and delay or prevent age-related diseases. One key example is the repurposing of metformin for conditions like PCOS and prediabetes. The FDA's focus is on clinical studies that demonstrate the prevention of age-related diseases, even if aging itself is not recognized as a disease. The study design for aging-related trials differs from traditional disease-specific trials, requiring fewer participants and opening avenues for pharmaceutical companies to develop drugs targeted at aging. Metformin, SGLT2 inhibitors, tyrosine kinase inhibitors, and GLP-1 inhibitors are highlighted as promising drugs in this regard.
The Role of Metformin and Potential Risks
The podcast explores the role of metformin in activating longevity switches like AMPK, which inhibits inflammation, activates sirtuins for DNA repair, and improves mitochondrial function. It also raises concerns about the potential risk of metformin inhibiting muscle growth and density in the context of weight training and preventing sarcopenia. The interplay between metformin, muscle mass, and muscle quality is discussed, highlighting changes in muscle gene expression and the potential trade-offs involved. The speaker emphasizes the importance of understanding the nuances and complexities of metformin's mechanisms of action and its effects on various aspects of health and aging.
Other Geroprotective Molecules and Future Prospects
The podcast touches upon other geroprotective molecules and drugs that are under research, such as NAD+ and rapamycin. It mentions the TAME trial, a template study for targeting aging, as well as ongoing initiatives like the SuperAges initiative and the FAST project, which aims to identify and validate biomarkers of aging and their response to treatment. The speaker emphasizes the need for clinical studies and the importance of deciphering the complex interconnections and potential synergies or antagonisms between different geroprotectors. Personal habits for health and longevity, including exercise, intermittent fasting, and adequate sleep, are also highlighted, with the speaker acknowledging individual variation and the need for personalized approaches based on one's own health and goals.
Dr. Nir Barzilai is a geroscientist, Chaired Professor of Medicine and Genetics, and the founder and principal investigator of the Einstein Nathan Shock Center and the Glenn Center for Excellence in Biology of Aging. He also studies families of centenarians that have provided genetic and biological insights on the protection against aging—with several drugs developed based, in part, on these paradigm-changing studies. He is also leading the TAME (Targeting/Taming Aging with Metformin) trial to prove to the FDA that aging can be delayed and to allow for next-generation interventions.
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In this episode we discuss (audio version / Apple Subscriber version):
The hallmarks of aging (9:01 / 7:10)
What causes the hallmarks of aging? (15:40 / 13:49)
Dr. Barzilai’s research on centenarians (23:16 / 21:25)
Why living to 100+ years is good for the economy (24:54 / 23:03)
What enables someone to live to 100 years old? (29:30 / 25:20)
Taking growth hormone and Metformin have different effects based on your age (36:58 / 32:48)
The connection between HDL cholesterol and longevity (43:36 / 39:26)
Dr. Barzilai’s research on Metformin (56:23 / 52:13)
How Metformin works in the body and on muscle growth (1:04:51 / 1:00:41)
Dr. Barzilai’s personal longevity (1:42:05 / 1:37:55)
