title: Mechanisms linking mtDNA damage and aging.
abstract: In the past century, considerable efforts were made to understand the role of mitochondrial DNA (mtDNA) mutations and of oxidative stress in aging. The classic mitochondrial free radical theory of aging, in which mtDNA mutations cause genotoxic oxidative stress, which in turn creates more mutations, has been a central hypothesis in the field for decades. In the past few years, however, new elements have discredited this original theory. The major sources of mitochondrial DNA mutations seem to be replication errors and failure of the repair mechanisms, and the accumulation of these mutations as observed in aged organisms seems to occur by clonal expansion and not to be caused by a reactive oxygen species-dependent vicious cycle. New hypotheses of how age-associated mitochondrial dysfunction may lead to aging are based on the role of reactive oxygen species as signaling molecules and on their role in mediating stress responses to age-dependent damage. Here, we review the changes that mtDNA undergoes during aging and the past and most recent hypotheses linking these changes to the tissue failure observed in aging.
authors.affiliation: Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Pinto
authors.affiliation: Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Cell Biology and Anatomy, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. Electronic address: cmoraes@med.miami.edu.
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Moraes
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: Aging; Free radicals; Mitochondria; MtDNA; Mutation