Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF)-expressing central pacemaker neurons led to similar loss of climbing performance as Clk AR. Reactive oxygen species accumulated more with age in Clk AR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. In contrast, Clk AR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing) than cyc 0 and tim 0, or than control flies under constant light.
We found that lifespan was similarly reduced in three arrhythmic mutants ( Clk AR, cyc 0 and tim 0) and in wild-type flies under constant light, which stops the clock. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity.
