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PMID: 19797661 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ribosomal protein S6 kinase 1 signaling regulates mammalian life span.

Science (New York, N.Y.) ·Vol. 326 ·No. 5949 ·2009-10-02 ·Pages 140-4

Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson IC, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ

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.

MeSH Terms
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
Chemicals
Insulin Protein Kinases mTOR protein, mouse Ribosomal Protein S6 Kinases, 90-kDa Rps6ka1 protein, mouse TOR Serine-Threonine Kinases AMP-Activated Protein Kinases
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Selman Colin
Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK.
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
References (27)
27 references, click to expand
  1. Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways.
    Aging Cell. 2006 Apr;5(2):119-26 PMID: 16626391
  2. Functionally significant insulin-like growth factor I receptor mutations in centenarians.
    Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3438-42 PMID: 18316725
  3. Biomarkers of aging: prediction of longevity by using age-sensitive T-cell subset determinations in a middle-aged, genetically heterogeneous mouse population.
    J Gerontol A Biol Sci Med Sci. 2001 Apr;56(4):B180-6 PMID: 11283189
  4. Separating cause from effect: how does insulin/IGF signalling control lifespan in worms, flies and mice?
    J Intern Med. 2008 Feb;263(2):179-91 PMID: 18226095
  5. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans.
    Curr Biol. 2007 Oct 9;17(19):1646-56 PMID: 17900900
  6. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice.
    FASEB J. 2008 Mar;22(3):807-18 PMID: 17928362
  7. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity.
    Nature. 2009 Apr 23;458(7241):1056-60 PMID: 19262508
  8. Temporal linkage between the phenotypic and genomic responses to caloric restriction.
    Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5524-9 PMID: 15044709
  9. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans.
    Genes Dev. 2004 Dec 15;18(24):3004-9 PMID: 15574588
  10. Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1.
    Cell Metab. 2006 Jun;3(6):393-402 PMID: 16753575
  11. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity.
    Nature. 2004 Sep 9;431(7005):200-5 PMID: 15306821
  12. Metformin slows down aging and extends life span of female SHR mice.
    Cell Cycle. 2008 Sep 1;7(17):2769-73 PMID: 18728386
  13. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
    Nature. 2009 Jul 16;460(7253):392-5 PMID: 19587680
  14. Aging and survival: the genetics of life span extension by dietary restriction.
    Annu Rev Biochem. 2008;77:727-54 PMID: 18373439
  15. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice.
    Nature. 2003 Jan 9;421(6919):182-7 PMID: 12483226
  16. S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase.
    Cell Metab. 2007 Jun;5(6):476-87 PMID: 17550782
  17. Impact of reduced insulin-like growth factor-1/insulin signaling on aging in mammals: novel findings.
    Aging Cell. 2008 Jun;7(3):285-90 PMID: 18346217
  18. AMPK and PPARdelta agonists are exercise mimetics.
    Cell. 2008 Aug 8;134(3):405-15 PMID: 18674809
  19. S6 kinase inactivation impairs growth and translational target phosphorylation in muscle cells maintaining proper regulation of protein turnover.
    Am J Physiol Cell Physiol. 2007 Aug;293(2):C712-22 PMID: 17494629
  20. AMPK: an emerging drug target for diabetes and the metabolic syndrome.
    Cell Metab. 2009 May;9(5):407-16 PMID: 19416711
  21. Changes in bone structure and mass with advancing age in the male C57BL/6J mouse.
    J Bone Miner Res. 2002 Jun;17(6):1044-50 PMID: 12054159
  22. Insulin sensitivity as a key mediator of growth hormone actions on longevity.
    J Gerontol A Biol Sci Med Sci. 2009 May;64(5):516-21 PMID: 19304940
  23. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans.
    Aging Cell. 2007 Feb;6(1):111-9 PMID: 17266680
  24. Molecular links between aging and adipose tissue.
    Int J Obes (Lond). 2005 Mar;29 Suppl 1:S36-9 PMID: 15711582
  25. Rapamycin protects against high fat diet-induced obesity in C57BL/6J mice.
    J Pharmacol Sci. 2009 Apr;109(4):496-503 PMID: 19372632
  26. The pharmacology of mTOR inhibition.
    Sci Signal. 2009 Apr 21;2(67):pe24 PMID: 19383975
  27. Nutrient sensing in the mTOR/S6K1 signalling pathway.
    Biochem Soc Trans. 2007 Apr;35(Pt 2):236-8 PMID: 17371247
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1177221
Published
2009-10-02
Pages
140-4
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4954603
Subset
IM
Grants
Medical Research Council · G108/551 · United Kingdom
Medical Research Council · G0800339 · United Kingdom
Wellcome Trust · 066750 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBS/E/B/0000M979 · United Kingdom
Medical Research Council · MC_U120027537 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBS/E/B/0000C236 · United Kingdom
Medical Research Council · MC_U117531708 · United Kingdom
Medical Research Council · MC_U120097114 · United Kingdom
Corrections
ErratumIn
-
CommentIn
PMID: 19797648
External Links
PubMed source DOI: 10.1126/science.1177221 PMC Full Text View journal details
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