Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span

作者：Colin Selman, Jennifer M. A. Tullet, Daniela Wieser, Elaine E. Irvine, Steven J. Lingard, Agharul I. Choudhury, Marc Claret, Hind Al‐Qassab, Danielle F. Carmignac, Faruk Ramadani, Angela L. Woods, Iain C. A. F. Robinson, Eugene F. Schuster, Rachel Louise Batterham, Sara C. Kozma, George Thomas, David Carling, Klaus Okkenhaug, Janet M. Thornton, Linda Partridge, David Gems, Dominic J. Withers · 发表于：Science · 年份：2009 · DOI：10.1126/science.1177221 · 被引用次数：1141 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、FOXO transcription factor regulation、Metabolism, Diabetes, and Cancer

Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.