In this episode, we interview Dr. Nir Barzilai. We discuss the field of gero-therapeutics, the hallmarks of aging, and gender differences in aging. We review his work on centenarians and what they can teach us about the genetics of longevity. Finally, we delve into metformin, its use as an anti-aging therapy, its mechanism of action and the TAME trial, on which he is the primary investigator. This conversation was recorded on March 26, 2021.
Spotify | Apple Podcasts | Google Podcasts | YouTube
Check out the American Federation of Aging, where you can learn more about the latest in aging-related research.
Who is Nir Barzilai?
Dr. Nir Barzilai is the founding director of the Institute for Aging Research and an expert in the genetics of longevity. He is a professor in the departments of Medicine and Genetics at the Albert Einstein College of Medicine. He is the recipient of numerous awards and grants. He has published over 230 peer-reviewed papers, reviews, and textbook chapters. He is also the author of the book Age Later.
What are the Hallmarks of Aging?
Cell – “The Hallmarks of Aging” (2013)
Abstract: “Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases…These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.”
Centenarian studies:
The Longevity Genes Project is geared at understanding which genetic factors contribute to exceptionally long life. The project focuses on Ashkenazi “super agers”–people between the ages of 95 and 112–to determine how their genetics differ from controls without exceptional longevity. In addition, the study follows the children of “super agers” with matched controls.
What is Metformin?
Metformin (Glucophage) is a biguanide that is a first-line treatment for type 2 diabetes. While it has many mechanisms of action, its primary mechanisms of action are believed to be (1) decreasing hepatic glucose production by inhibiting gluconeogenesis, (2) inhibiting complex I of the electron transport chain, and (3) inhibiting the mammalian target of rapamycin (mTOR) signaling pathway. It is the 4th most prescribed medication in the United States. Metformin use is associated with a reduction in the incidence of cancer. It is also associated with reductions in cognitive decline and Alzheimer’s among diabetics.
If you are interested in learning more about how metformin attenuates the hallmarks of aging, Nir Barzilai wrote a paper in cell metabolism: Benefits of Metformin in Attenuating the Hallmarks of Aging (2020).
UK Study on Metformin:
Conclusions: “Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non‐diabetic controls. Those treated with sulphonylurea [sic] had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first‐line therapy and implies that metformin may confer benefit in non‐diabetes.”
What is the TAME Trial?
The Targeting Aging with Metformin (TAME) Trial is a placebo-controlled clinical trial designed to determine whether taking metformin delays the development or progression of age-related chronic diseases, including heart disease, cancer, and dementia. The study population will include 3,000 individuals at 14 sites across the U.S. who are between the ages of 65-79. Patients will receive either 1500mg Metformin daily or a placebo for up to 6 years.
