Ribosomal protein S6 kinase 1 signaling regulates mammalian life span.

Authors: Selman, Colin; Tullet, Jennifer M A; Wieser, Daniela; Irvine, Elaine; Lingard, Steven J; Choudhury, Agharul I; Claret, Marc; Al-Qassab, Hind; Carmignac, Danielle; Ramadani, Faruk; Woods, Angela; Robinson, Iain C A; Schuster, Eugene; Batterham, Rachel L; Kozma, Sara C; Thomas, George; Carling, David; Okkenhaug, Klaus; Thornton, Janet M; Partridge, Linda; Gems, David; Withers, Dominic J

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.

Keywords: AMP-Activated Protein Kinases/metabolism; Adipose Tissue, White/metabolism; Aging/*physiology; Animals; Bone Density; Caloric Restriction; Female; Gene Deletion; Gene Expression; Gene Expression Regulation; Insulin/metabolism; Liver/metabolism; Longevity/*physiology; Male; Mice; Mice, Inbred C57BL; Motor Activity; Muscle, Skeletal/metabolism; Protein Kinases/metabolism; Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism; *Signal Transduction; T-Lymphocyte Subsets/immunology; TOR Serine-Threonine Kinases; Transcription, Genetic
Journal: Science
Volume: 326
Issue: 5949
Pages: 140-4
Date: Oct. 3, 2009
PMID: 19797661
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Citation:

Selman, Colin, Tullet, Jennifer M A, Wieser, Daniela, Irvine, Elaine, Lingard, Steven J, Choudhury, Agharul I, Claret, Marc, Al-Qassab, Hind, Carmignac, Danielle, Ramadani, Faruk, Woods, Angela, Robinson, Iain C A, Schuster, Eugene, Batterham, Rachel L, Kozma, Sara C, Thomas, George, Carling, David, Okkenhaug, Klaus, Thornton, Janet M, Partridge, Linda, Gems, David, Withers, Dominic J (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326: 140-4.


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