Reconsidering the Role of Mitochondria in Aging

摘要: Background: Mitochondrial dysfunction has long been considered a major contributor to aging and age-related diseases. Harman ’s Free Radical Theory of Aging postulated that somatic mitochondrial DNA mutations accumulate over the life span cause excessive production reactive oxygen species damage macromolecules impair cell tissue function. Indeed, studies have shown maximal oxidative capacity declines with age while increases. Harman’s hypothesis seriously challenged by recent showing evoke metabolic health longevity, perhaps through hormetic mechanisms include autophagy. The purpose this review is scan ever-growing literature on mitochondria from perspective research try identify priority questions should be addressed in future research. Methods: A systematic search peer -reviewed was performed using PubMed. Search terms included (i) or mitochondrial; (ii) aging, ageing, older adults elderly; (iii) species, dynamics, proteostasis, cytosol, mitochondrial-associated membranes, redox homeostasis, electron transport chain, chain efficiency, epigenetic regulation, heteroplasmy. Results: importance mitoc hondrial biology as trait d’union between basic pathogenesis diseases stronger than ever, although emphasis moved other aspects physiology, including biogenesis turnover, energy sensing, apoptosis, senescence, calcium dynamics. Conclusions: Mitochondria could play k ey role pathophysiology earlier stages some events lead phenotype. Therefore, will increasingly targeted prevent treat chronic promote healthy aging.