title: Complex-I-ty in aging.
abstract: The role of mitochondrial complex I in aging has been studied in both C. elegans and Drosophila, where RNAi knock down of specific complex I subunits has been shown to extend lifespan. More recently, studies in Drosophila have shown that an increase in mitochondrial activity, including complex I-like activity, can also slow aging. In this review, we discuss this apparent paradox. Improved maintenance of mitochondrial activity, mitochondrial homeostasis, may be responsible for lifespan extension in both cases. Decreased electron transport chain activity caused by reducing complex I subunit expression prompts an increase in stress response signaling that leads to enhanced mitochondrial homeostasis during aging. Increased complex I activity, as well as mitochondrial biogenesis, is expected to both directly counteract the decline in mitochondrial health that occurs during aging and may also increase cellular NAD(+) levels, which have been linked to mitochondrial homeostatic mechanisms through activation of sirtuins. We suggest that manipulations that increase or decrease complex I activity both converge on improved mitochondrial homeostasis during aging, resulting in prolonged lifespan.
authors: Department of Biology, Harvey Mudd College, Claremont, CA, 91711, USA, jaehur@gmail.com.
authors: Jae H
authors: JH
authors: Hur
authors: Devon A
authors: DA
authors: Stork
authors: David W
authors: DW
authors: Walker
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009243:NAD / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D024101:Mitochondrial Proteins; D009243:NAD; D042967:Electron Transport Complex I