Models for the evolution of senescence assume that genes with age-specific effects act independently of one another. Although recent empirical data show that longevity is influenced in part by interactions between genes, there are currently few data on whether epistasis influences age-specific components of mortality. To gauge if and how interactions affect age-specific traits, we incorporated the Drosophila visible marker mutations ebony, forked, and purple into seven wild-caught strains of D. melanogaster to examine gene x genetic background interactions. We found significant natural genetic variation for longevity and baseline mortality rates. Gene x genetic background interactions were prevalent not only for longevity but also for baseline mortality rates and age-specific mortality rates. We conclude that gene x genetic background epistasis is prevalent for aging-related traits and could play a significant role in the evolution of aging. These results suggest that future genetic models for the evolution of aging should incorporate the effects of epistasis.