Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

• DOI: 10.1371/journal.pgen.1006507
• Publication Date: 2017-01-10T13:25:13Z
• Authors: Alexandra Vaccaro; Abdul-Raouf Issa; Laurent Seugnet; Serge Birman; André Klarsfeld
• Keywords: Mushroom bodies

Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In organisms, oxidative stress aging negatively impact the circadian system sleep. Conversely, loss of clock decreases resistance to stress, may reduce lifespan speed up brain neurodegeneration. Here we examined effects disruptions on locomotor longevity Drosophila. We found that was similarly reduced three arrhythmic mutants (ClkAR, cyc0 tim0) wild-type flies under constant light, which stops clock. contrast, ClkAR showed significantly faster age-related deficits (as monitored by startle-induced climbing) than tim0, or light. Reactive oxygen species accumulated more age mutant brains, but this did not appear contribute accelerated decline mutant. Clk, Cyc, inactivation RNA interference pigment-dispersing factor (PDF)-expressing central pacemaker neurons led similar climbing performance as ClkAR. restoring Clk function these cells sufficient rescue phenotype, independently behavioral rhythmicity. Accelerated required expression PDF receptor correlated an apparent dopaminergic posterior protocerebral lateral 1 (PPL1) clusters. This neuronal rescued when mutation placed apoptosis-deficient background. Impairing dopamine synthesis a single pair PPL1 innervate mushroom bodies otherwise flies. Our results therefore reveal novel circadian-independent requirement for maintain subset avoid premature