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Ribosomal protein S6 kinase 1 signaling regulates mammalian life span

Colin Selman1, Jennifer M A Tullet, Daniela Wieser

  • 1Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK.

Science (New York, N.Y.)
|October 3, 2009
PubMed

Insights

Deleting ribosomal S6 protein kinase 1 (S6K1) in mice extended lifespan and improved healthspan, mimicking effects of caloric restriction. This suggests S6K1 and AMPK manipulation could offer protection against aging diseases.

Area of Science:

  • Aging research
  • Molecular biology
  • Metabolic pathways

Background:

  • Caloric restriction (CR) is known to extend lifespan and protect against age-related diseases in mammals.
  • The precise molecular mechanisms underlying CR's benefits, particularly its impact on nutrient-sensing pathways, remain incompletely understood.

Purpose of the Study:

  • To investigate the role of ribosomal S6 protein kinase 1 (S6K1) in aging and age-related pathologies.
  • To explore whether manipulating S6K1 could replicate the beneficial effects of caloric restriction.

Main Methods:

  • Utilized genetically modified mice with S6K1 deletion.
  • Analyzed lifespan, age-related pathologies (bone, immune, motor function, insulin sensitivity), and gene expression patterns.
  • Compared gene expression profiles with those induced by caloric restriction and AMPK activation.

Main Results:

  • S6K1 deletion in mice significantly increased lifespan.
  • Mice lacking S6K1 exhibited resistance to multiple age-related dysfunctions, including bone, immune, and motor deficits, and improved insulin sensitivity.
  • Gene expression changes in S6K1-deleted mice mirrored patterns observed in caloric restriction and with adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation.

Conclusions:

  • Ribosomal S6 protein kinase 1 (S6K1) plays a crucial role in regulating healthy mammalian lifespan.
  • Therapeutic targeting of S6K1 and AMPK pathways may offer a strategy to mimic caloric restriction's benefits.
  • Such interventions hold potential for broad protection against diverse diseases of aging.

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