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A metabolic model for life span determination in Caenorhabditis elegans.

Rea S, Johnson TE.
Institute for Behavioral Genetics, University of Colorado, Boulder, 1480 30th Street, Boulder, CO 80309, USA. srea@colorado.edu

Several studies with the nematode Caenorhabditis elegans have made the unexpected discovery that certain hypomorphic mutations in genes encoding mitochondrial proteins result in life span extension. These mutations appear to act independently of the other known pathway that regulates life span extension, the dauer-specifying insulin/IGF-1-like pathway. Here we present a hypothesis that unifies the effects of these two classes of genes on longevity. The central concept is that energy generation in C. elegans occurs by differential flux through two coexisting mitochondrial metabolic pathways-aerobic respiration and fermentative malate dismutation. In the latter process, fumarate is terminally reduced at complex II to succinate. We suggest that most, if not all, long-lived mutants in C. elegans utilize malate dismutation, a byproduct of which is the generation of fewer radical species.