#148 - Richard Miller, M.D., Ph.D.: The gold standard for testing longevity drugs: the Interventions Testing Program

Drive with Dr. Peter Attia

Podcast Notes Introduction Interventions Testing Program developed the gold standard protocol of using mice to testing lifespan drugs“I don’t really care what causes aging. What I care about is what can postpone all the different aspects of aging. Once you rephrase the question you are well on the way to designing experimental paradigms which address the serious question.” – Dr. Richard MillerA good lifespan drug will extend life in the oldest animals in the treatment group compared to the oldest animals in the control groupA big surprise is that rapamycin and acarbose have positive lifespan effects even when administered late in life Most longevity drugs have differential effects in males and femalesRegulation of glucose in males seems to be a potential driver in increasing lifespan and healthspan in mice models Positive impact on longevity: 17-alpha estradiol (in males only), acarbose, rapamycin, canagliflozin (SGLT-2 inhibitor)

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Richard Miller is a professor of pathology and the Director of the Center for Aging Research at the University of Michigan. He is one of the architects of the NIA-funded Interventions Testing Programs (ITPs) animal study test protocol. In this episode, Rich goes through the results of the long list of molecules tested by the ITP—including rapamycin, metformin, nicotinamide riboside, an SGLT-2 inhibitor called canagliflozin, and more. Many of the discussed outcomes have had surprising outcomes—both positive and negative findings.

We discuss:

Rich’s interest in aging, and how Hayflick’s hypothesis skewed aging research (3:45); Dispelling the myth that aging can’t be slowed (15:00); The Interventions Testing Program—A scientific framework for testing whether drugs extend lifespan in mice (29:00); Testing aspirin in the first ITP cohort (38:45); Rapamycin: results from ITP studies, dosing considerations, and what it tells us about early- vs. late-life interventions (44:45); Acarbose as a potential longevity agent by virtue of its ability to block peak glucose levels (1:07:15); Resveratrol: why it received so much attention as a longevity agent, and the takeaways from the negative results of the ITP study (1:15:45); The value in negative findings: ITP studies of green tea extract, methylene blue, curcumin, and more (1:24:15); 17α-Estradiol: lifespan effects in male mice, and sex-specific effects of different interventions (1:27:00); Testing ursolic acid and hydrogen sulfide: rationale and preliminary results (1:33:15); Canagliflozin (an SGLT2 inhibitor): exploring the impressive lifespan results in male mice (1:35:45); The failure of metformin: reconciling negative results of the ITP with data in human studies (1:42:30); Nicotinamide riboside: insights from the negative results of the ITP study (1:48:45); The three most important takeaways from the ITP studies (1:55:30); Philosophies on studying the aging process: best model organisms, when to start interventions, which questions to ask, and more (1:59:30); Seven reasons why pigs can't fly (2:08:00); and More. Learn more: https://peterattiamd.com/   Show notes page for this episode: https://peterattiamd.com/RichardMiller    Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/   Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/   Connect with Peter on Facebook | Twitter | Instagram.