Transgenes in the analysis of life span and fitness

Drosophila P element-mediated transformation can be used to determine wheth er and how a specific gene contributes to demographic components of fitness . Motivated by the problem of senescence, researchers have applied this app roach to genes thought to affect survival through processes of somatic main tenance. Cu/Zn-superoxide dismutase and catalase reduce the flux of reactiv e oxygen molecules that are thought to be a central cause of aging. EF1 alp ha is a component of the protein synthesis machine; deterioration of this h ousekeeping function is a potential contributor to senescence. Molecular ch aperones such as the heat shock protein hsp70 are multifunctional molecules that affect a cell's response to acute stress. In some models, senescence results from the cumulative effects of stress, and heat shock proteins may regulate the progress of this deterioration. Transformations with the candi date genes of these proteins were used in independent studies to measure th e effect of overexpression on longevity; positive results were reported. He re, I discuss the robustness of these results. I use the studies of superox ide dismutase, catalase, and EF1 alpha to illustrate how the mutagenic effe cts of inserts confound our interpretations. I present new data from a repo rted study of hsp70 overexpression to show how engineered constructs can be used to overcome mutagenic artifacts through the controlled excision of se quences or alleles. The data for hsp70 provide the first strong molecular e vidence that somatic maintenance affects longevity. Finally, future potenti al uses of transformation with Drosophila are discussed. I consider how met abolic control theory predicts that overexpression of genes for enzymes of intermediary metabolism is not likely to produce analytically useful change s in components of fitness.