C. Elegans Longevity Pathways Converge to Decrease Mitochondrial Membrane Potential

Energy production via oxidative phosphorylation generates a mitochondrial membrane potential (ΔΨm) across the inner membrane. In this work, we show that a lower ΔΨm 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 ΔΨm than wild type animals. The lower ΔΨm 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 ΔΨm. Furthermore, lifespan can be significantly extended with the uncoupler carbonylcyanide-3-chlorophenylhydrazone (CCCP), which dissipates ΔΨm. We conclude that longevity pathways converge on the mitochondria and lead to a decreased ΔΨm. Our results are consistent with the ‘uncoupling to survive’ hypothesis, which states that dissipation of the ΔΨm will extend lifespan.