Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span

Colin Selman(University College London), Jennifer M. A. Tullet(MRC Unit for Lifelong Health and Ageing), Daniela Wieser(European Bioinformatics Institute), Elaine E. Irvine(University College London), Steven J. Lingard(University College London), Agharul I. Choudhury(University College London), Marc Claret(University College London), Hind Al‐Qassab(University College London), Danielle Carmignac(General Medical Council), Faruk Ramadani(Babraham Institute), Angela Woods(Medical Research Council), Iain C. A. F. Robinson(General Medical Council), Eugene F. Schuster(European Bioinformatics Institute), Rachel L. Batterham(University College London), Sara C. Kozma(University of Cincinnati), George Thomas(University of Cincinnati), David Carling(Medical Research Council), Klaus Okkenhaug(Babraham Institute), Janet M. Thornton(European Bioinformatics Institute), Linda Partridge(MRC Unit for Lifelong Health and Ageing), David Gems(MRC Unit for Lifelong Health and Ageing), Dominic J. Withers(University College London)
Science
October 1, 2009
10.1126/science.1177221
Cited by 1,117

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.

Related Papers

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
David E. Harrison, Randy Strong, Z. Dave Sharp et al.|Nature|2009|3.7k
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Carles Cantó, Zachary Gerhart‐Hines, Jérôme N. Feige et al.|Nature|2009|3.2k
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Martin Holzenberger, Joëlle Dupont, Bertrand Ducos et al.|Nature|2002|2.1k
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Sung Hee Um, Francesca Frigerio, Mitsuhiro Watanabe et al.|Nature|2004|1.6k
AMPK and PPARδ Agonists Are Exercise Mimetics
Vihang A. Narkar, Michael Downes, Ruth T. Yu et al.|Cell|2008|1.2k