#359 ‒ How metabolic and immune system dysfunction drive the aging process, the role of NAD, promising interventions, aging clocks, and more | Eric Verdin, M.D.

Geroscience research emphasizes the critical roles of the immune system and metabolic health as rate-limiting factors in human longevity. Dr. Eric Verdin, CEO of the Buck Institute for Research on Aging, highlights how the "distributed" nature of the central nervous and immune systems makes their decline particularly impactful on overall lifespan. Key metabolic drivers of aging include the transition from clean fuel utilization, like ketones, to "dirtier" glucose metabolism, which triggers harmful insulin and IGF-1 signaling. The conversation explores the decline of the thymus and its impact on T-cell diversity, alongside the role of CD38 in depleting NAD levels during aging. While NAD precursors like NMN and NR show promise in animal models, their human application remains complex due to potential side effects like elevated homocysteine. Emerging diagnostic tools, including organ-specific proteomic clocks and the DunedinPACE metric, offer new ways to measure biological aging and the efficacy of interventions like exercise and GLP-1 agonists.