title: Regulation of lifespan by the mitochondrial electron transport chain: reactive oxygen species-dependent and reactive oxygen species-independent mechanisms.
abstract: CONCLUSIONS
  Aging is a consequence of the accumulation of cellular damage that impairs the capacity of an aging organism to adapt to stress. The Mitochondrial Free Radical Theory of Aging (MFRTA) has been one of the most influential ideas over the past 50 years. The MFRTA is supported by the accumulation of oxidative damage during aging along with comparative studies demonstrating that long-lived species or individuals produce fewer mitochondrial reactive oxygen species and have lower levels of oxidative damage.
  
  
  BACKGROUND
  Recently, however, species that combine high oxidative damage with a longer lifespan (i.e., naked mole rats) have been described. Moreover, most of the interventions based on antioxidant supplementation do not increase longevity, as would be predicted by the MFRTA. Studies to date provide a clear understanding that mitochondrial function regulates the rate of aging, but the underlying mechanisms remain unclear.
  
  
  RESULTS
  Here, we review the reactive oxygen species (ROS)-dependent and ROS-independent mechanisms by which mitochondria can affect longevity. We discuss the role of different ROS (superoxide, hydrogen peroxide, and hydroxyl radical), both as oxidants as well as signaling molecules. We also describe how mitochondria can regulate longevity by ROS-independent mechanisms. We discuss alterations in mitochondrial DNA, accumulation of cellular waste as a consequence of glyco- and lipoxidative damage, and the regulation of DNA maintenance enzymes as mechanisms that can determine longevity without involving ROS.
  
  
  CONCLUSIONS
  We also show how the regulation of longevity is a complex process whereby ROS-dependent and ROS-independent mechanisms interact to determine the maximum lifespan of species and individuals.
authors.affiliation: 1 Institute of Biomedical Technology and Tampere University Hospital , University of Tampere, Tampere, Finland .
authors.forename: Filippo
authors.initials: F
authors.lastname: Scialo
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Mallikarjun
authors.forename: Rhoda
authors.initials: R
authors.lastname: Stefanatos
authors.forename: Alberto
authors.initials: A
authors.lastname: Sanz
mesh_terms: D000818:Animals; D004579:Electron Transport; D006801:Humans; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species