Purpose of review 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.
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-1α) 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.
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.