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. RECENT FINDINGS: 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. SUMMARY: 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.
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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: Stephen D Anton; Adam J Woods; Tetso Ashizawa; Diana Barb; Thomas W Buford; Christy S Carter; David J Clark; Ronald A Cohen; Duane B Corbett; Yenisel Cruz-Almeida; Vonetta Dotson; Natalie Ebner; Philip A Efron; Roger B Fillingim; Thomas C Foster; David M Gundermann; Anna-Maria Joseph; Christy Karabetian; Christiaan Leeuwenburgh; Todd M Manini; Michael Marsiske; Robert T Mankowski; Heather L Mutchie; Michael G Perri; Sanjay Ranka; Parisa Rashidi; Bhanuprasad Sandesara; Philip J Scarpace; Kimberly T Sibille; Laurence M Solberg; Shinichi Someya; Connie Uphold; Stephanie Wohlgemuth; Samuel Shangwu Wu; Marco Pahor Journal: Ageing Res Rev Date: 2015-10-14 Impact factor: 10.895
Authors: Julianna H Huang; Anna-Maria Joseph; Vladimir Ljubicic; Sobia Iqbal; David A Hood Journal: J Gerontol A Biol Sci Med Sci Date: 2010-01-02 Impact factor: 6.053
Authors: D M Thomson; J D Brown; N Fillmore; S K Ellsworth; D L Jacobs; W W Winder; C A Fick; S E Gordon Journal: J Physiol Date: 2009-03-09 Impact factor: 5.182