The circadian clock and its neuro-protective role during aging
We experience the potent effects of circadian clocks when we travel across time zones and feel jet-lagged! These clocks generate circa-24h rhythms in sleep/activity, cognitive abilities, and hormone levels, besides other metabolic and cellular rhythms. Recent studies suggest that disruption of rhythms is associated with premature aging and age-related pathologies in mammals. Since the clock mechanism is highly conserved between mammals and the fruitfly Drosophila melanogaster, we use fruitflies to study circadian clocks and aging. We determined that aging is associated with disrupted rest/activity patterns, and lengthening of the free-running period of locomotor activity, suggesting weakened clock mechanism. Indeed, aging flies showed dampened mRNA oscillations of the essential clock gene period (per) in heads.
Aging is associated with accumulation of oxidative damage in the nervous system. Because impaired circadian rhythms are observed in many neurological diseases, we hypothesized that loss of clocks may contribute to neurodegeneration in aging flies. To test this, we combined a null mutation in the clock gene period (per01) that disrupts circadian rhythms, with a mutation in the gene sniffer (sni1), which displays oxidative stress-induced neurodegeneration. We report that per01 sni1 double mutants showed accelerated brain-damage, impaired vertical mobility, and accumulated damaged proteins. Additionally, loss of circadian rhythms by both genetic and environmental manipulations significantly reduced the lifespan of sni1 mutant. Our study suggests that circadian clocks are involved in neuro-protective pathways which may curb damage to the nervous system during aging. These findings may serve as a starting point for translational research in humans.