Prevention of flight activity prolongs the life span of the housefly, Musca domestica, and attenuates the age-associated oxidative damage to specificmitochondrial proteins

The purpose of this study was to explore the mechanisms by which oxidative stress affects the aging process. The hypothesis that the rate of accumulat ion of oxidative damage to specific mitochondrial proteins is linked to the life expectancy of animals was tested in the housefly. The rate of oxygen consumption and life expectancy of the flies were experimentally altered by confining the flies in small jars, where they were unable to fly. Preventi on of flight activity decreased the rate of oxygen utilization of flies and almost tripled their life span as compared to those permitted to fly. Rate of mitochondrial H2O2 generation at various ages was lower in the low acti vity flies than in the high activity flies. Oxidative damage to mitochondri al proteins, adenine nucelotide translocase, and aconitase, detected as car bonyl modifications, was attenuated; and the loss in their functional activ ity occurring with age was retarded in the long-lived low activity flies as compared to the short-lived high activity flies. The two proteins were pre viously identified to be the only mitochondrial proteins exhibiting age-rel ated increases in carbonylation. Results support the hypothesis that accrua l of oxidative damage to specific protein targets and the consequent loss o f their function may constitute a mechanism by which oxidative stress contr ols the aging process. (C) 2000 Elsevier Science Inc.