ABSTRACT Support is requested for a Keystone Symposia conference entitled Molecular Basis of Healthy Aging, organized by Drs. Amy Wagers, Saul Villeda and Salvador Aznar Benitah. The conference will be held in Breckenridge, Colorado from March 26-29, 2023. This conference will explore the biological mechanisms that regulate trajectories of aging and enhance organismal resilience. The program will include discussions on lessons learned from research on multiple organ systems, organisms, and experimental model systems, with a broad scope spanning molecular to systems approaches. Emphasis will be placed on recent technological and conceptual innovations and translational opportunities that have opened new frontiers in the effort to protect health during aging. Other topics of focus will include discussion of the accelerated trajectories of aging that may arise due to stress, disease, genetic, epigenetic and external (sleep, nutrition, light and other pollution) influences, as well as emerging therapeutic opportunities that exploit these mechanisms, including gene therapies, senolytic, senomorphic and immune modulating drugs, and cellular replacement therapies. One unique feature of this program will be the inclusion of expert speakers employing “big data” and machine learning approaches for meta-analyses of aging trajectories and biomarkers. Finally, this conference will be held jointly with Mitochondrial Dysfunction: From Ultra-rare Diseases to Aging, which will address key questions surrounding mitochondrial pathogenesis and bring a powerful perspective on the function of these critical organelles across a continuum of development, growth and aging. It is anticipated these interactions will drive exciting cross- fertilization of ideas drawing lessons and mechanisms from both rare genetic disorders and more common diseases of advancing age.