Forward and reverse selection for longevity in Drosophila is characterizedby alteration of antioxidant gene expression and oxidative damage patterns

Patterns of antioxidant gene expression and of oxidative damage were measur ed throughout the adult life span of a selected long-lived strain (La) of D rosophila melanogaster and compared to that of their normal-lived progenito r strain (Ra). Extended longevity in the La strain is correlated with enhan ced antioxidant defense system gene expression, accumulation of CuZnSOD pro tein, and an increase in ADS enzyme activities. Extended longevity is stron gly associated with a significantly increased resistance to oxidative stres s. Reverse-selecting this long-lived strain for shortened longevity (RevLa strain) yields a significant decrease in longevity accompanied by reversion to normal levels of its antioxidant defense system gene expression pattern s and antioxidant enzyme patterns. The significant effects of forward and r everse selection in these strains seem limited to the ADS enzymes; 11 other enzymes with primarily metabolic functions show no obvious effect of selec tion on their activity levels whereas six other enzymes postulated to play a role in flux control may actually be involved in NADPH reoxidation and th us support the enhanced activities of the ADS enzymes. Thus, alterations in the longevity of these Drosophila strains are directly correlated with cor responding alterations in; 1) the mRNA levels of certain antioxidant defens e system genes; 2) the protein level of at least one antioxidant defense sy stem gene; 3) the activity levels of the corresponding antioxidant defense system enzymes, and 4) the ability of the organism to resist the histologic al damage arising from oxidative stress. (C) 2000 Elsevier Science Inc. All rights reserved.