Limited lifespan and senescence are near-universal phenomena. These quantitative traits exhibit variation in natural populations due to the segregation of many interacting loci and from environmental effects. Due to the complexity of the genetic control of lifespan and senescence, our understanding of the genetic basis of variation in these traits is incomplete. Our goal is to identify causal genes associated with increased lifespan and postponed reproductive senescence in Drosophila melanogaster by functional analyses of genetically divergent genes between five long-lived (O) lines selected for postponed reproductive senescence and five unselected (B) lines. Preliminary data assessing productivity of the reciprocal crosses of the O and B lines suggest that genes influencing reproductive senescence are maternally-controlled. Therefore, all of the candidate genes tested are expressed in the ovaries of females. To determine which of these candidate genes exhibit a quantitative change in lifespan or reproductive productivity, I have assessed lifetime reproduction of candidate genes from the Vienna collection of RNAi lines in which gene expression is knocked down in ovaries. Identifying specific genes affecting increased lifespan and delayed reproductive senescence will increase our knowledge of the evolutionary role of naturally segregating populations on overall fitness and may provide potential targets for therapeutic intervention to delay senescence in populations with increasing lifespans.