Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage.
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.
Van Raamsdonk
Jeremy Michael
JM
Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.
Meng
Yan
Y
Camp
Darius
D
Yang
Wen
W
Jia
Xihua
X
Bénard
Claire
C
Hekimi
Siegfried
S
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
D005609:Free Radicals; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase
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