Distinct aging-vulnerable and -resilient trajectories of specific motor circuit functions in oxidation- and temperature-stressed Drosophila.

In Drosophila, molecular pathways affecting longevity have been extensively studied. However, corresponding neurophysiological changes underlying aging-related functional and behavioral deteriorations remain to be fully explored. We examined different motor circuits in Drosophila across the lifespan and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. In the giant-fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex, we observed relatively mild deterioration toward the end of lifespan. In contrast, more substantial age-dependent modifications were seen in the plasticity of GF afferent processing, specifically in use-dependence and habituation properties. In addition, there were profound changes in different afferent circuits that drive flight motoneuron activities, including flight pattern generation and seizure spike discharges evoked by electroconvulsive stimulation. Importantly, in high temperature (HT)-reared flies (29 °C), the general trends in these age-dependent trajectories were largely maintained, albeit over a compressed time scale, lending support for the common practice of HT rearing for expediting Drosophila aging studies. We discovered that shortened lifespans in Cu/Zn superoxide dismutase (Sod) mutant flies were accompanied by altered aging trajectories in motor circuit properties distinct from those in HT-reared flies, highlighting differential effects of oxidative vs temperature stressors. This work helps to identify several age-vulnerable neurophysiological parameters that may serve as quantitative indicators for assessing genetic and environmental influences on aging progression in Drosophila Significance statementComparisons of the aging trajectories of performance changes of several motor circuits in Drosophila revealed remarkably heterogeneous age-progressions. We identified "aging-resilient" and "aging-vulnerable" circuits in both normal control and flies with shortened lifespans due to either elevated rearing temperature or oxidative stress. Motor circuit components including flight motor neuron and the giant-fiber pathway responsible for the escape reflex showed only mild functional decline, whereas distinct trajectories throughout lifespan were seen in the flight pattern generator, interneuron inputs to the giant-fiber system, and circuits generating seizure discharge patterns. Notably, high-temperature rearing generally compressed aging trajectories while Sod mutation-induced oxidative stress led to distinct patterns of motor defects. Together, these results elucidate potentially salient neurophysiological markers for aging in flies.