A causal link between respiration and senescence in Podospora anserina

Senescence, a progressive degenerative process leading to age-related incre ase in mortality, is found in most eukaryotes, However, the molecular event s underlying aging remain largely unknown. Understanding how longevity is r egulated is a fundamental problem. Here we demonstrate that the respiratory function is a key factor that contributes to shortening lifespan of the fi lamentous fungus Podospora anserina, In this organism, senescence is system atically associated with mitochondrial DNA instabilities. We show that inac tivation of the nuclear COX5 gene encoding subunit V of the cytochrome c ox idase complex leads to the exclusive use of the alternative respiratory pat hway and to a decrease in production of reactive oxygen species. This inact ivation results in a striking increase of longevity associated with stabili zation of the mitochondrial chromosome. Moreover, accumulation of several s enescence-specific mitochondrial DNA molecules is prevented in this nuclear mutant, These findings provide direct evidence of a causal link between mi tochondrial metabolism and longevity in Podospora anserina.