The Contributions of Mitochondria to Longevity

Manipulating the machinery of mitochondria - the respiratory chain that turns food into the chemical ATP that is used to power cellular biochemistry - can extend healthy life in a variety of species. Here, researchers dig deeper into the mechanisms by which this happens, finding that there are more than one: "In Caenorhabditis elegans longevity is increased by a partial loss-of-function mutation in the mitochondrial complex III subunit gene isp-1. Longevity is also increased by RNAi against the expression of a variety of mitochondrial respiratory chain genes, including isp-1, but it is unknown whether the isp-1(qm150) mutation and the RNAi treatments trigger the same underlying mechanisms of longevity. We have identified nuo-6(qm200), a mutation [that] reduces the function of complex I and, like isp-1(qm150), results in low oxygen consumption, slow growth, slow behavior, and increased lifespan. We [compared] nuo-6(qm200) [to] nuo-6(RNAi) and found them to be distinct in crucial ways, including patterns of growth and fertility, behavioral rates, oxygen consumption, ATP levels, autophagy, [as] well as expression of superoxide dismutases, mitochondrial heat shock proteins, and other gene expression markers. RNAi treatments appear to generate a stress and autophagy response, while the genomic mutation alters electron transport and reactive oxygen species metabolism. ... Most importantly, we found that [the] lifespan increase induced by nuo-6(RNAi) is fully additive to that induced by isp-1(qm150), and the increase induced by isp-1(RNAi) is fully additive to that induced by nuo-6(qm200). Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20346072

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