On Drosophila aging: Lifespan plasticity, social-behavioral influences, and neurophysiological indices

Characterized by physiological decline, the aging process is nevertheless plastic as demonstrated in lifespan extension conferred by single-gene mutations as well as epigenetic factors. The documented beneficial effects of social interactions on aging have prompted us to investigate its genetic basis in Drosophila melanogaster. We found that short-lived Drosophila Sod mutants, defective in the anti-oxidant enzyme Cu/Zn superoxide dismutase (CuZnSOD), displayed a robust lifespan extension, along with improved stress resistance and motor ability, upon co-housing with active flies of longer lifespan or younger age. Genetic, surgical and environmental manipulations revealed motor and sensory components in behavioral interactions required for Sod fly lifespan extension. Moreover, co-housed Sod flies showed improved muscle physiology and giant fiber (GF) pathway motor responses, plus elevated MnSOD activity.;We performed a first comprehensive characterization of the electrophysiological changes along the GF sensory-motor pathway in aged wild-type and Sod flies. In contrast to a progressive decline in the compound eye electroretinogram, indicating diminishing GF visual input in aged flies, the threshold and latency of the motor output remained unaltered, reflecting the maintenance of the robust GF-mediated escape function during aging. Significantly, the refractory period and following-frequency of the GF output showed increased variability in aged populations. Unlike these basic motor responses, habituation and electroconvulsion-induced seizure revealed greatly altered neural plasticity in aged flies. We found accelerated habituation in the afferent to the GF pathway and enhanced seizure-like discharges in a motor program, which underscore altered stability and activity-dependent plasticity in the relevant brain and thoracic neural circuits during aging. These alterations were further enhanced by stresses associated with high temperature and Sod mutations.;We studied quiver (qvr) mutations that cause hypersensitive to oxidative stress and complete lethality in qvr; Sod double mutants. EMS- and P element-induced new qvr alleles identified a candidate gene CG33472, encoding a novel peptide. Double-mutant combinations of qvr with K + channel mutations Sh, Hk and eag result in extreme hyperexcitability. Thus, the qvr gene product may link redox regulation and ion channel function in the phenomena of stress response and nerve excitability.