A Drosophila model for age-associated changes in sleep:wake cycles

Abstract

One of the most consistent behavioral changes that occurs with age in humans is the loss of sleep consolidation. This can be quite disruptive and yet little is known about its underlying basis. To better understand the effects of aging on sleep:wake cycles, we sought to study this problem in Drosophila melanogaster, a powerful system for research on aging and behavior. By assaying flies of different ages as well as monitoring individual flies constantly over the course of their lifetime, we found that the strength of sleep:wake cycles decreased and that sleep became more fragmented with age in Drosophila. These changes in sleep:wake cycles became faster or slower with manipulations of ambient temperature that decreased or increased lifespan, respectively, demonstrating that they are a function of physiological rather than chronological age. The effect of temperature on lifespan was not mediated by changes in overall activity level or sleep amount. Flies treated with the oxidative stress-producing reagent paraquat showed a breakdown of sleep:wake cycles similar to that seen with aging, leading us to propose that the accumulation of oxidative damage with age contributes to the changes in rhythm and sleep. Together, these findings establish Drosophila as a valuable model for studying age-associated sleep fragmentation and breakdown of rhythm strength, and indicate that these changes in sleep:wake cycles are an integral part of the physiological aging process.aging ͉ circadian rhythms ͉ sleep fragmentation

Molecular Analysis of Sleep: Wake Cycles inDrosophila

“…4). In contrast, wild-type flies retain rhythms in the presence of paraquat for up to 3 weeks (Koh et al 2006b). These effects of FOXO occur in the fat coexpressed with clock proteins in the central brain (Stanewsky et al 1998;Emery et al 2000).…”

“…Our fly studies suggest that although circadian regulation may be disrupted with age, this is probably not the sole cause of the sleep disturbances in old flies. Young tim 01 mutants have more fragmented sleep than their wild-type counterparts, but their sleep patterns also get worse with age (Koh et al 2006b). Because tim 01 flies have no clock to begin with, their age-induced defects must occur elsewhere, most likely in the homeostatic system.…”

“…Given that rest:activity rhythms are driven by the central clock in the brain, these data demonstrate that a peripheral metabolic tissue can affect clock function in the brain. Because aging is typically associated with an increase in oxidative stress, and we have found that circadian rhythms also break down with age (Koh et al 2006b), we also examined the effects of age on foxo mutants. As one might expect, they show a premature breakdown of rhythms (Zheng et al 2007).…”

“…We recently discovered another aspect of fly rest that is shared with mammalian sleep-they both get fragmented with age. As flies get older, they show increased daytime sleep, decreased nighttime sleep, and decreased duration of sleep bouts (Koh et al 2006b). Thus, in general, they have trouble maintaining a consolidated sleep state.…”

Sleep disruption, oxidative stress, and aging: New insights from fruit flies

“…In their study, Koh et al (9) find that aging does not decrease total sleep duration. Moreover, they show that manipulations of ambient temperature that increase or decrease lifespan also decrease and increase sleep fragmentation, respectively, but do not affect total sleep duration or overall levels of locomotor activity.…”