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Dr. Matt Kaeberlein is a globally recognized expert on the biology of aging and recurring on The Drive. In this episode, Matt explains his research findings on nutrition as it relates to aging and longevity, including the results from his recent review article in Science. From there, he and Peter dive deep into the literature on calorie restriction (CR), explaining the nuance, benefits for lifespan and healthspan, and potential downsides of CR. He discusses the epigenetic changes that occur with age and potential benefits and downsides of epigenetic reprogramming, often viewed as a panacea for reversing aging. Matt also explains the impact of dietary protein on aging, including the interesting dichotomy around how protein, a critical macronutrient, and rapamycin, a geroprotective molecule, have opposite effects on mTOR. Additionally, he talks about low-protein vs. high-protein diets and their effects on muscle mass and mortality, as well as the impact of IGF-1 signaling and growth hormone on lifespan.

We discuss:

• Challenges with understanding the effects of nutrition and studying interventions for aging [3:30];
• How Peter's and Matt's convictions on nutrition and thoughts optimal health have evolved [8:15];
• Calorie restriction for improving lifespan in animal models [16:15];
• Utility of epigenetic clocks and possibility of epigenetic reprogramming [22:00];
• Mutations and changes to the epigenome with aging [31:45];
• Epigenetic reprogramming: potential benefits and downsides and whether it can work in every organ/tissue [35:15];
• First potential applications of anti-aging therapies and tips for aging well [43:00];
• Impact of calorie restriction on the immune system, muscle mass, and strength [47:00];
• Insights from famous calorie restriction studies in rhesus macaques [55:00];
• An evolutionary perspective of the human diet [1:03:45];
• Antiaging diets: Separating fact from fiction—Matt's 2021 review in Science [1:12:30];
• Mouse models of time-restricted feeding in the context of calorie restriction [1:19:30];
• Nutritional interventions that consistently impact lifespan in mice, and concerns around efficacy in humans [1:27:00];
• Differing impact of calorie restriction when started later in life [1:31:00];
• Lifespan extension with rapamycin in older mice [1:37:15];
• Relationship between protein intake and aging, and mouse studies showing protein restriction can extend lifespan [1:43:30];
• Impact of protein intake on mTOR, and why inhibition of mTOR doesn't cause muscle loss [1:50:45];
• Low-protein vs. high-protein diets and their effects on muscle mass, mortality, and more [1:55:30];
• The impact of IGF-1 signaling and growth hormone on lifespan [2:06:30];
• Parting thoughts on the contribution of nutrition to healthspan and lifespan [2:19:45];
• More.

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