Abstract
Since the discovery of the first genes to regulate aging three decades ago, it has been clear that the insulin/IGF-1 (Insulin-like Growth Factor 1) signaling pathway can regulate lifespan. Since then, studies in organisms including C. elegans and mice have found that many dietary, genetic, and pharmaceutical interventions that reduce signaling downstream of insulin/IGF-1 promote longevity and healthspans. However, the molecular and physiological mechanisms which mediate these effects have proven elusive. In this session, we will discuss new findings regarding the sensing of nutrients and the regulation of healthspan and longevity downstream of insulin/IGF-1 signaling, concentrating on the mTOR (mechanistic Target Of Rapamycin) protein kinase and the FOXO (Forkhead box O) family of transcription factors. Topics will include: 1) the molecular mechanisms by which mTOR complex 1 (mTORC1) signaling is regulated by amino acids; 2) how storage of glucose as trehalose can extend longevity via a FOXO-dependent mechanism; 3) the hithero unappreciated role of mTOR complex 2 (mTORC2) in longevity and healthspan; and 4) the role of FOXO transcription factors in maintaining healthy stem cells.