Ribosomal protein S6 kinase 1 signaling regulates mammalian life span.

Full 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.

Author information

Author/s: Selman, Colin (C); Tullet, Jennifer M A (JM); Wieser, Daniela (D); Irvine, Elaine (E); Lingard, Steven J (SJ); Choudhury, Agharul I (AI); Claret, Marc (M); Al-Qassab, Hind (H); Carmignac, Danielle (D); Ramadani, Faruk (F); Woods, Angela (A); Robinson, Iain C A (IC); Schuster, Eugene (E); Batterham, Rachel L (RL); Kozma, Sara C (SC); Thomas, George (G); Carling, David (D); Okkenhaug, Klaus (K); Thornton, Janet M (JM); Partridge, Linda (L); Gems, David (D); Withers, Dominic J (DJ);

Affiliation: Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK.

Grants: (Agency:Biotechnology and Biological Sciences Research Council) ; (Agency:Medical Research Council) ; (Agency:Wellcome Trust)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Science (New York, N.Y.) (Science), published in United States. (Language: eng)

Reference: 2009-Oct; vol 326 (issue 5949) : pp 140-4

Dates: Created 2009/10/02; Completed 2009/10/16;

PMID: 19797661, status: MEDLINE (last retrieval date: 10/16/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Science. 2009 Oct 2;326(5949):55-6. (PMID: 19797648)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

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

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
Transcription, Genetic

Associated Chemicals: Insulin (11061-68-0) ; mTOR protein (EC 2.7.1.-) ; Protein Kinases (EC 2.7.1.37) ; Ribosomal Protein S6 Kinases, 90-kDa (EC 2.7.1.37) ; AMP-Activated Protein Kinases (EC 2.7.11.1) ; Rps6ka1 protein, mouse (EC 2.7.11.1)

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