Abstract
Aging is accompanied by loss of motor function driven by mitochondrial oxidative stress. To examine how genotype and sex modulate this process, we exposed Oregon-R (wild-type) and vestigial (wing-deficient) Drosophila of both sexes to chronic paraquat a mitochondrial stressor generating sustained ROS production at 0, 10, or 20 mM. We tracked climbing performance from day 5-50 alongside survival. Paraquat impaired locomotion dose- dependently, with effects modified by genotype and sex (four-way ANOVA, all p < 0.001). Under control conditions, behavioral half-life (T50) occurred at 21.4 days in Oregon-R males and 25.7 days in females. Vestigial flies declined earlier: 14.8 days (males), 18.3 days (females). At 20 mM, T50 fell 48-53% across groups. Female advantage persisted at 10 mM but narrowed at 20 mM, especially in vestigial flies. Survival mirrored functional decline. The T50-to-lifespan interval compressed under severe stress: 18-28 days (controls) versus 8-12 days (20 mM). Functional-survival coupling was strong (r = 0.87, p < 0.001). Oxidative stress accelerates functional aging through mechanisms shaped by genotype and sex. Climbing performance predicts healthspan and may serve as a translational biomarker for neuromuscular aging.
