Ribosomal protein S6 Kinase 1 signaling regulates mammalian life span
Selman, C. and Tullet, J.M.A. and Wieser, D. and Irvine, E. and Lingard, S.J. and Choudhury, A.I. and Claret, M. and Al-Qassab, H. and Carmignac, D. and Ramadani, F. and Woods, A. and Robinson, I.C.A. and Schuster, E. and Batterham, R.L. and Kozma, S.C. and Thomas, G. and Carling, D. and Okkenhaug, K. and Thornton, Janet M. and Partridge, L. and Gems, D. and Withers, D.J. (2009) Ribosomal protein S6 Kinase 1 signaling regulates mammalian life span. Science 326 (5949), pp. 140-144. ISSN 0036-8075.
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.
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Date Deposited:||04 Aug 2010 14:09|
|Last Modified:||17 Apr 2013 12:17|
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