C. elegans longevity pathways converge to decrease mitochondrial membrane potential

Energy production via oxidative phosphorylation generates a mitochondrial membrane potential (Delta Psi(m)) across the inner membrane. In this work, we show that a lower Delta Psi(m) is associated with increased lifespan in Caenorhabditis elegans. The long-lived mutants daf-2(ei370), age-1(hx546), clk-1(qm30), isp-1(qm150) and eat-2(ad465) all have a lower Delta Psi(m) than wild type animals. The lower Delta Psi(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 Delta Psi(m). Furthermore, lifespan can be significantly extended with the uncoupler carbonylcyanide-3-chlorophenylhydrazone (CCCP), which dissipates Delta Psi(m). We conclude that longevity pathways converge on the mitochondria and lead to a decreased Delta Psi(m). Our results are consistent with the uncoupling to survive hypothesis, which states that dissipation of the Delta Psi(m) will extend lifespan. (C) 2009 Elsevier Ireland Ltd. All rights reserved.