title: Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage.
abstract: On the basis of the free radical and rate of living theories of aging, it has been proposed that decreased metabolism leads to increased longevity through a decreased production of reactive oxygen species (ROS). In this article, we examine the relationship between mitochondrial energy metabolism and life span by using the Clk mutants in Caenorhabditis elegans. Clk mutants are characterized by slow physiologic rates, delayed development, and increased life span. This phenotype suggests that increased life span may be achieved by decreasing energy expenditure. To test this hypothesis, we identified six novel Clk mutants in a screen for worms that have slow defecation and slow development and that can be maternally rescued. Interestingly, all 11 Clk mutants have increased life span despite the fact that slow physiologic rates were used as the only screening criterion. Although mitochondrial function is decreased in the Clk mutants, ATP levels are normal or increased, suggesting decreased energy utilization. To determine whether the longevity of the Clk mutants results from decreased production of ROS, we examined sensitivity to oxidative stress and oxidative damage. We found no evidence for systematically increased resistance to oxidative stress or decreased oxidative damage in the Clk mutants despite normal or elevated levels of superoxide dismutases. Overall, our findings suggest that decreased energy metabolism can lead to increased life span without decreased production of ROS.
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.
authors.forename: Jeremy Michael
authors.initials: JM
authors.lastname: Van Raamsdonk
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Darius
authors.initials: D
authors.lastname: Camp
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.forename: Xihua
authors.initials: X
authors.lastname: Jia
authors.forename: Claire
authors.initials: C
authors.lastname: Bénard
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hekimi
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005221:Fatigue / Q000235:genetics / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D008017:Life Expectancy; D008136:Longevity / Q000235:genetics* / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D005609:Free Radicals; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase
references.citation: J Exp Biol. 2005 May;208(Pt 9):1717-30
references.pmid: 15855403
references.citation: Mech Ageing Dev. 2004 Jun;125(6):455-64
references.pmid: 15178135
references.citation: Curr Biol. 2001 Dec 11;11(24):1934-44
references.pmid: 11747819
references.citation: J Biol Chem. 2003 Jun 13;278(24):21678-84
references.pmid: 12670948
references.citation: J Biol Chem. 2001 Mar 16;276(11):7713-6
references.pmid: 11244089
references.citation: Biochem Biophys Res Commun. 2005 May 13;330(3):839-43
references.pmid: 15809072
references.citation: Exp Gerontol. 2009 Dec;44(12):784-91
references.pmid: 19808088
references.citation: Dev Cell. 2001 Nov;1(5):633-44
references.pmid: 11709184
references.citation: Free Radic Biol Med. 2007 Aug 15;43(4):477-503
references.pmid: 17640558
references.citation: J Gerontol. 1956 Jul;11(3):298-300
references.pmid: 13332224
references.citation: Mech Ageing Dev. 2009 Jul;130(7):461-5
references.pmid: 19442682
references.citation: J Biol Chem. 2009 Jul 24;284(30):20364-74
references.pmid: 19478076
references.citation: Curr Biol. 1999 May 6;9(9):493-6
references.pmid: 10330373
references.citation: Genetics. 2007 Dec;177(4):2063-74
references.pmid: 18073424
references.citation: Development. 2001 Oct;128(20):4045-55
references.pmid: 11641227
references.citation: Mech Ageing Dev. 2002 Sep;123(11):1447-56
references.pmid: 12425951
references.citation: Genetics. 1995 Dec;141(4):1351-64
references.pmid: 8601479
references.citation: Trends Genet. 2001 Dec;17(12):712-8
references.pmid: 11718925
references.citation: Science. 1997 Feb 14;275(5302):980-3
references.pmid: 9020081
references.citation: Aging Cell. 2007 Aug;6(4):489-503
references.pmid: 17608836
references.citation: Methods Cell Biol. 1995;48:81-96
references.pmid: 8531747
references.citation: Exp Gerontol. 2001 Nov;36(10):1609-17
references.pmid: 11672983
references.citation: Nat Genet. 2003 Jan;33(1):40-8
references.pmid: 12447374
references.citation: J Biol Chem. 2003 Dec 5;278(49):49555-62
references.pmid: 14517217
references.citation: Nature. 1993 Dec 2;366(6454):461-4
references.pmid: 8247153
references.citation: EMBO J. 1999 Apr 1;18(7):1783-92
references.pmid: 10202142
references.citation: Mech Ageing Dev. 2009 Mar;130(3):173-8
references.pmid: 19059428
references.citation: Genetics. 1995 Mar;139(3):1247-59
references.pmid: 7768437
references.citation: Science. 2002 Dec 20;298(5602):2398-401
references.pmid: 12471266
references.citation: Genetics. 2001 Sep;159(1):147-57
references.pmid: 11560893
references.citation: Free Radic Biol Med. 2009 Jan 1;46(1):105-9
references.pmid: 18977291
references.citation: Cell Metab. 2007 Apr;5(4):233-5
references.pmid: 17403368
references.citation: Biochem J. 2009 Jan 1;417(1):1-13
references.pmid: 19061483
references.citation: J Biol Chem. 2004 Dec 24;279(52):54479-86
references.pmid: 15269213
references.citation: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8084-9
references.pmid: 15141086
references.citation: Mech Ageing Dev. 2009 Jun;130(6):370-6
references.pmid: 19428456
references.citation: Genetics. 1974 May;77(1):71-94
references.pmid: 4366476
references.citation: Genes Dev. 2008 Dec 1;22(23):3236-41
references.pmid: 19056880
references.citation: PLoS Genet. 2009 Feb;5(2):e1000361
references.pmid: 19197346
references.citation: Genetics. 1993 Apr;133(4):897-917
references.pmid: 8462849
references.citation: J Biol Chem. 2006 Jan 20;281(3):1332-7
references.pmid: 16287813
references.citation: Exp Gerontol. 2008 Jun;43(6):520-9
references.pmid: 18406553
references.citation: Methods Mol Biol. 2009;554:165-81
references.pmid: 19513674
references.citation: PLoS Biol. 2007 Oct 2;5(10):e259
references.pmid: 17914900
references.citation: Science. 2003 Dec 5;302(5651):1779-82
references.pmid: 14657502
references.citation: J Biol Chem. 2001 Jun 8;276(23):20551-8
references.pmid: 11278828
references.citation: Mutat Res. 1990 May-Jul;237(3-4):165-71
references.pmid: 2233820
references.citation: Science. 1996 May 17;272(5264):1010-3
references.pmid: 8638122
references.citation: Cell. 2007 Dec 28;131(7):1248-59
references.pmid: 18160036
references.citation: Genetics. 2004 Oct;168(2):845-54
references.pmid: 15514058
references.citation: Genes Dev. 2005 Oct 15;19(20):2424-34
references.pmid: 16195414
references.citation: Genetics. 1988 Jan;118(1):75-86
references.pmid: 8608934