title: Mammalian Mitochondria and Aging: An Update.
abstract: Mitochondria were first postulated to contribute to aging more than 40 years ago. During the following decades, multiple lines of evidence in model organisms and humans showed that impaired mitochondrial function can contribute to age-associated disease phenotypes and aging. However, in contrast to the original theory favoring oxidative damage as a cause for mtDNA mutations, there are now strong data arguing that most mammalian mtDNA mutations originate as replication errors made by the mtDNA polymerase. Currently, a substantial amount of mitochondrial research is focused on finding ways to either remove or counteract the effects of mtDNA mutations with the hope of extending the human health- and lifespan. This review summarizes the current knowledge regarding the formation of mtDNA mutations and their impact on mitochondrial function. We also critically discuss proposed pathways interlinked with mammalian mtDNA mutations and suggest future research strategies to elucidate the role of mtDNA mutations in aging.
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany.
authors.forename: Timo E S
authors.initials: TES
authors.lastname: Kauppila
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany.
authors.forename: Johanna H K
authors.initials: JHK
authors.lastname: Kauppila
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address: larsson@age.mpg.de.
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D004194:Disease / Q000235:genetics; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: ROS; acetylation; aging; biogenesis; mitophagy; mtDNA