Mitochondria, telomeres and cell senescence.
The accumulation of oxidative damage is one of the most widely accepted causes of ageing. Mitochondrial dysfunction, in particular damage to the mitochondrial DNA has been hypothesised, more than thirty years ago, as responsible for increased production of reactive oxygen species (ROS) and, thus, as one possible causal factor for ageing. There is now a wealth of data that supports this hypothesis, which is mostly derived from models considering the ageing of post-mitotic or slowly dividing cells in vivo. One major cellular model of ageing, however, is replicative senescence, the irreversible loss of division potential of somatic cells after a more or less constant number of cell divisions. Not much data exists concerning the role of mitochondria in this model. Here, we review evidence supporting an involvement of mitochondria in replicative senescence and a possible link to telomere shortening.
Passos
João F
JF
Henry Wellcome Laboratory for Biogerontology Research, Newcastle University, Newcastle NE4 6BE, UK.
von Zglinicki
Thomas
T
D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D004247:DNA / Q000502:physiology; D004272:DNA, Mitochondrial / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016615:Telomere / Q000502:physiology*; D014475:Uncoupling Agents / Q000378:metabolism
D004272:DNA, Mitochondrial; D005609:Free Radicals; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D004247:DNA