C. elegans longevity pathways converge to decrease mitochondrial membrane potential

Energy production via oxidative phosphorylation generates a mitochondrial membrane potential (ΔΨ_m) across the inner membrane. In this work, we show that a lower ΔΨ_m is associated with increased lifespan in Caenorhabditis elegans. The long-lived mutants daf-2(e1370), age-1(hx546), clk-1(qm30), isp-1(qm150) and eat-2(ad465) all have a lower ΔΨ_m than wild type animals. The lower ΔΨ_m of daf-2(e1370) is daf-16 dependent, indicating that the insulin-like signaling pathway not only regulates lifespan but also mitochondrial energetics. RNA interference (RNAi) against 17 genes shown to extend lifespan also decrease ΔΨ_m. Furthermore, lifespan can be significantly extended with the uncoupler carbonylcyanide-3-chlorophenylhydrazone (CCCP), which dissipates ΔΨ_m. We conclude that longevity pathways converge on the mitochondria and lead to a decreased ΔΨ_m. Our results are consistent with the ‘uncoupling to survive’ hypothesis, which states that dissipation of the ΔΨ_m will extend lifespan.