Mitochondrial function as a determinant of life span.
Average human life expectancy has progressively increased over many decades largely due to improvements in nutrition, vaccination, antimicrobial agents, and effective treatment/prevention of cardiovascular disease, cancer, etc. Maximal life span, in contrast, has changed very little. Caloric restriction (CR) increases maximal life span in many species, in concert with improvements in mitochondrial function. These effects have yet to be demonstrated in humans, and the duration and level of CR required to extend life span in animals is not realistic in humans. Physical activity (voluntary exercise) continues to hold much promise for increasing healthy life expectancy in humans, but remains to show any impact to increase maximal life span. However, longevity in Caenorhabditis elegans is related to activity levels, possibly through maintenance of mitochondrial function throughout the life span. In humans, we reported a progressive decline in muscle mitochondrial DNA abundance and protein synthesis with age. Other investigators also noted age-related declines in muscle mitochondrial function, which are related to peak oxygen uptake. Long-term aerobic exercise largely prevented age-related declines in mitochondrial DNA abundance and function in humans and may increase spontaneous activity levels in mice. Notwithstanding, the impact of aerobic exercise and activity levels on maximal life span is uncertain. It is proposed that age-related declines in mitochondrial content and function not only affect physical function, but also play a major role in regulation of life span. Regular aerobic exercise and prevention of adiposity by healthy diet may increase healthy life expectancy and prolong life span through beneficial effects at the level of the mitochondrion.
Lanza
Ian R
IR
Division of Endocrinology, Endocrinology Research Unit, Mayo Clinic College of Medicine, Rochester, MN, USA.
Nair
K Sreekumaran
KS
D050154:Adiposity / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D031204:Caloric Restriction; D004272:DNA, Mitochondrial / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D006801:Humans; D008017:Life Expectancy; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D037761:Sirtuins / Q000502:physiology
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D037761:Sirtuins