Review of Genetic Investigations into the Aging Processes of Drosophila

Abstract

The field has progressed to the point where a genetic investigation of the aging processes in Drosophila can be viewed as constituting both a serious and a feasible research program. There now exists at least one single gene mutant which yields an accelerated aging phenotype, at least two single gene null mutants affecting enzymes implicated in regulating the aging process and resulting in premature death, and at least two strains created by artificial selection which produce extended-longevity phenotypes. In addition, genes such as adh have an indirect and interactive effect upon the animal's longevity and might also play an important role in the genetic regulation of this process. Although far from complete, some essential tools are now in place and are being used to answer some of the questions posed by Martin. Of the several theories put forth to explain aging in Drosophila, it appears as if the data best uphold the free radical and the protein synthesis/gene expression theories. It is entirely possible that these two theories are complementary aspects of a broader underlying process. The genetic mechanisms controlling these physiological processes clearly do so in concert with certain environmental factors. The net effect of their interactions may be the decreased synthetic and repair ability of the cell as suggested by Lamb and by Webster. It is probably true that aging and longevity are multicausal phenotypes. Our only hope of understanding such a complex phenotype is to dissect it genetically, one (or a few) genes at a time under rigidly controlled conditions. Thorough genetic description of each system will be the prerequisite to their molecular analysis. This will likely result in multiple explanations, ideally one for each system. Yet these multiple molecular genetic explanations may well enable us to see some commonality underlying the aging process in this organism. The fact that several different lines of evidence appear to be converging on a small number of theoretical explanations is an encouraging sign. We should also be heartened by the extraordinary increase in our knowledge of embryonic development in Drosophila as a result of just such a strategy. And we should not forget that the homeotic mutants which now play such a large role in the deciphering of embryogenesis were once classified as "complex loci" and that the then-accepted explanations gave no hint of the underlying molecular relationships. For now it is fair to conclude that aging in Drosophila may be viewed as a genetically-determined, environmentally-modulated, event-dependent process.(ABSTRACT TRUNCATED AT 400 WORDS)

Developmental variability and the limits of adaptation: Interactions with stress

“…The cell has an elaborate antioxidant defense system made up of enzymes and metabolites that inactivate free radicals. Simplistically, an inverse relationship between antioxidant defense activity and the amount of oxidative damage can be postulated, so that strains with a high antioxidant defense system should survive longer (Arking & Dudas, 1989). Under stressful environments where an immediate response is increased metabolic rate, the expectation therefore is elevated free radical production and an increase in abnormalities of all kinds including developmental ones.…”

Selection for Increased Longevity in <i>Drosophila melanogaster</i><i>:</i> A Reply to Lints

“…There is a difference in their response to larval density [19], There is a difference in their antioxidant mRNA levels and antioxidant enzyme levels [11,20]. All of these and more have been dis cussed in a number of readily available review articles [12,21,22]. There are in fact signifi cant biological differences between the sever al strains.…”

Healthy human aging: intrinsic and environmental factors

“…The time variable, however, determines the stages of life. Arking and Dudas (1989) showed that a more sophisticated understanding of "aging" had been achieved, since time is only an imperfect analogous of the physiological processes in the course of life until senescence. We should be able to use the alteration in physiological variables instead of using the calendar to measure aging.…”