Mitochondrial bioenergetic changes during development as an indicator of C. elegans health-span

Mild suppression of mitochondrial activity has beneficial effects across species. The nematode Caenorhabditis elegans is a versatile, genetically tractable model organism widely employed for aging studies, which has led to the identification of many of the known evolutionarily conserved mechanisms regulating lifespan. In C. elegans the pro-longevity effect of reducing mitochondrial function, for example by RNA interference, is only achieved if mitochondrial stress is applied during larval development. Surprisingly, a careful analysis of changes in mitochondrial functions resulting from such treatments during the developmental windows in which pro-longevity signals are programmed has never been carried out. Thus, although the powerful C. elegans genetics have led to the identification of different molecular mechanisms causally involved in mitochondrial stress control of longevity, specific functional mitochondrial biomarkers indicative or predictive of lifespan remain to be identified. To fill this gap, we systematically characterized multiple mitochondrial functional parameters at an early developmental stage in animals that are long-lived due to mild knockdown of twelve different mitochondrial proteins and correlated these parameters with animals’ lifespan. We found that basal oxygen consumption rate and ATP-linked respiration positively correlate with lifespan extension and propose the testable hypothesis that the Bioenergetic Health Index can be used as a proxy to predict health-span outcomes.