The common fruit fly, Drosophila melanogaster, is a well-characterized model for neurological disorders and is widely used to investigate the biology of aging, stress tolerance and pleiotropy. The foraging (for) gene encodes a cGMP-dependent protein kinase (PKG), which has been implicated in several behavioral phenotypes including feeding, sleep, learning and memory, and environmental stress tolerance. We used the well-established Drosophila activity monitor (DAM) to investigate the effects of the conserved NO/cGMP/PKG signaling pathway on functional senescence. Our results show that the polymorphic for gene confers protection during low oxygen stress at the expense of longevity and a decline in locomotor activity with age in D. melanogaster, which suggests a novel role for the PKG pathway in healthy aging and senescence.