Dr. Charles Brenner: How to Live Longer & Longevity Drugs Debate

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Matt and City of Hope Alfred E. Mann Family Foundation Chair of Diabetes and Cancer Metabolism Charles Brenner have had several public disagreements on social media. We love a good conversation between two distinguished scientists whose views may not entirely align, so we were pleased to host Charles on the Optispan Podcast for a discussion of topics in geroscience ranging from whether sirtuins are actually longevity regulators to the clinical utility of epigenetic age tests to the incentive structures around clinical trials. We also spent a chunk of time on NAD+ boosters, one of Charles' areas of expertise, and their relevance to aging and other conditions such as COVID-19.

Prior to his City of Hope appointment, Charles served on the faculties of Thomas Jefferson University, Dartmouth College, and the University of Iowa, where he was the Roy J. Carver Head of Biochemistry for 11 years. He currently serves as the Chief Scientific Advisor of the biotechnology company ChromaDex, which uses his nicotinamide riboside (NR) intellectual property. He is also a cofounder of biotechnology companies Alphina and Juvenis. Charles conducted postdoctoral research at Brandeis University and received a PhD and a B.A. from Stanford University and Wesleyan University respectively.

0:00 Introduction
1:31 The geroscience hypothesis and the degree to which it is actionable
5:24 Longevity genes, growth hormone, "longevity docs"
10:19 A mutual love of dogs + why dogs are important for geroscience research + drug development for dogs
14:43 Would getting an effective longevity intervention to work in dogs or another model organism increase Charles' confidence that a similar intervention could exist for humans?
16:41 Laron syndrome and biological aging
19:20 Social/biological consequences of Laron syndrome, hormone replacement therapy
26:07 The benefits and risks of longevity drugs/interventions/supplements
29:40 Matt's views on rapamycin/mTOR signaling and aging
35:19 Charles' concerns with rapamycin side effects + Matt's response, risk-reward analyses
41:39 Athletes' juicing and n=1 experiments
44:45 Charles on the biology of NAD+ + how NAD+ levels change with age, in nursing mothers, in COVID-19
1:06:00 The most compelling clinical trials for NR + clinical trial challenges
1:14:55 Why hasn't anyone started certain clinical trials?
1:20:20 Is there a biological argument for making nicotinamide mononucleotide (NMN), but not other NAD+ boosters, a pharmaceutical drug?
1:27:15 NAD+ boosters and kidney pathology
1:30:46 The potential therapeutic spectrum of the various NAD+ precursors
1:38:30 The relative use cases for niacin, nicotinamide, NR, NMN
1:40:25 Does Charles take NR?
1:41:18 Charles' thoughts on sirtuins and their role in the biology of aging + longevity genes
1:52:51 Natural selection for lifespan + optimizing genes for longevity
1:54:06 Charles' lab's project on FGF21
1:53:32 Back to sirtuins
2:05:22 What the data on people taking NR look like + pediatric cancer survivors/other unusual subpopulations and accelerated aging
2:12:13 Biological age clocks
2:17:24 Charles' final thoughts on NAD+ boosters + wrapping up

Producers: Tara Mei, Nicholas Arapis
Video Editor: Jacob Keliikoa

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