Ribosomal protein S6 kinase 1 signaling regulates mammalian life span

Colin Selman, 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 PartridgeDavid Gems, Dominic J Withers

Research output: Contribution to journalArticle

726 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)140-144
Number of pages5
JournalScience
Volume326
Issue number5949
DOIs
Publication statusPublished - 2 Oct 2009

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Keywords

  • AMP-activated protein kinases
  • adipose tissue, white
  • aging
  • animals
  • bone density
  • caloric restriction
  • female
  • gene deletion
  • gene expression
  • gene expression regulation
  • insulin
  • liver
  • longevity
  • male
  • mice
  • mice, inbred C57BL
  • motor activity
  • muscle, skeletal
  • protein kinases
  • ribosomal protein S6 kinases, 90-kDa
  • signal transduction
  • T-lymphocyte subsets
  • transcription, genetic

Cite this

Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., ... Withers, D. J. (2009). Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science, 326(5949), 140-144. https://doi.org/10.1126/science.1177221