Mitochondrial dysfunction and age.
OBJECTIVE
Mitochondrial dysfunction is commonly thought to result from oxidative damage that leads to defects in the electron transport chain (ETC). In this review, we highlight new research indicating that there are early changes in mitochondrial function that precede ETC defects and are reversible thereby providing the possibility of slowing the tempo of mitochondrial aging and cell death.


RESULTS
Increased mitochondrial uncoupling - reduced adenosine triphosphate (ATP) produced per O2 uptake - and cell ATP depletion are evident in human muscle nearly a decade before accumulation of irreversible DNA damage that causes ETC defects. New evidence points to reduction in activators of biogenesis (e.g. PGC-1alpha) and to degradation of mitochondria allowing accumulation of molecular and membrane damage in aged mitochondria. The early dysfunction appears to be reversible based on improved mitochondrial function in vivo and elevated gene expression levels after exercise training.


CONCLUSIONS
New molecular and in vivo findings regarding the onset and reversibility of mitochondrial dysfunction with age indicate the potential: 1) for diagnostic tools to identify patients at risk for severe irreversible defects later in life; and 2) of an intervention to delay the tempo of aging and improve the quality of life of the elderly.
Conley
Kevin E
KE
Department of Radiology, University of Washington Medical Center, Seattle, Washington, USA. kconley@u.washington.edu
Marcinek
David J
DJ
Villarin
Jason
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D019069:Cell Respiration; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D000255:Adenosine Triphosphate; D010100:Oxygen