| Literature DB >> 19797661 |
Colin Selman1, Jennifer M A Tullet, Daniela Wieser, Elaine Irvine, Steven J Lingard, Agharul I Choudhury, Marc Claret, Hind Al-Qassab, Danielle Carmignac, Faruk Ramadani, Angela Woods, Iain C A Robinson, Eugene Schuster, Rachel L Batterham, Sara C Kozma, George Thomas, David Carling, Klaus Okkenhaug, Janet M Thornton, Linda Partridge, David Gems, Dominic J Withers.
Abstract
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.Entities:
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Year: 2009 PMID： 19797661 PMCID： PMC4954603 DOI： 10.1126/science.1177221
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728