In this conversation, Daniel Belkin and Mitch Belkin interview Jean Hébert, PhD about aging, brain plasticity, and progressive neocortical replacement. They discuss one hallmark of aging—extracellular matrix damage—as well as how tissue replacement is a possible solution to aging. In addition, they explore the practicalities of progressive neocortex replacement, dopaminergic neuron transplants in Parkinson’s patients, and Professor Hébert’s work on stroke.
Jean Hebert, PhD, is a Professor of Neuroscience and Genetics at the Albert Einstein College of Medicine where he focuses on age-related brain degeneration in the adult neocortex. He is one of the world’s leading researchers on brain cell and tissue replacement. He is the author of the book Replacing Aging.
In this conversation, Daniel Belkin and Mitch Belkin speak with Sekar Kathiresan, MD, about using gene editing medications to treat cardiovascular disease. We discuss Dr. Kathiresan’s company Verve Therapeutics, which has pioneered a lipid nanoparticle delivery system of a CRISPR-based gene editing technology. We delve into the pathophysiology of cardiovascular disease, the role played by LDL and the LDL receptor in atherosclerosis, the genetics underlying monogenic and polygenic risk for myocardial infarction, CRISPR and the future of gene editing technologies, and Verve’s ongoing phase I trial of a PCSK9 gene editing medication (VERVE-101) in humans.
Dr. Sekar Kathiresan, a cardiologist, geneticist, and the CEO and co-founder of Verve Therapeutics. Verve Therapeutics is a company pioneering a new approach to the treatment of cardiovascular disease with single-dose gene editing medications. Prior to co-founding Verve, he served as the director of the Massachusetts General Hospital Center for Genomic Medicine and was a Professor of Medicine at Harvard Medical School.
In this External Medicine Podcast interview, Daniel Belkin and Mitch Belkin speak with Yuri Deigin about aging, which he argues is fundamentally an epigenetic phenomenon. They discuss partial reprogramming using Yamanaka factors, evolutionary explanations of aging, and recent in vivo experiments which suggest that aging is partially reversible. They also touch on mRNA vaccines, specifically to address allegations about the cytotoxicity of the spike protein and concerns about infertility discussed on Bret Weinstein’s Dark Horse Podcast with Steve Kirsch and Robert Malone, MD, recorded on June 11th 2021. This conversation with Yuri Deigin was recorded on June 25th, 2021.
Yuri Deigin is a biotech entrepreneur with a background in pharmaceutical development. He received degrees in computer science and mathematics from the University of Toronto and an MBA from Columbia University. He is the CEO of Youthereum Genetics, a company which aims to translate epigenetic rejuvenation therapies to humans.
Yuri was an early proponent of the SARS-CoV-2 lab leak hypothesis, the idea that the virus may have inadvertently escaped from a lab. In April 2020, he published a detailed genomic analysis of SARS-CoV-2. In that article, Yuri discusses the virus’s furin cleavage site, genetic similarities and differences with its closest relative (RaTG13), and the similarities between the virus’s receptor binding motif and that of a pangolin respiratory virus. He also explores the gain-of-function research program at the Wuhan Institute of Virology. Unfortunately, we did not have time in this conversation to delve into this hotly debated topic.
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.
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.
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 areduction in the incidence of cancer. It is also associated with reductions in cognitive decline and Alzheimer’s among diabetics.
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.
