The goal of this project is to determine the mechanisms underlying age-associated fragmentation of sleep:wake cycles and the relevance of this fragmentation to the aging process. The organism that will be used for these studies is the fruit fly,Drosophila melanogaster. In preliminary studies, we have found that the strength of the sleep:wake rhythm declines with age, such that the duration of sleep bouts decreases while the number of sleep bouts and brief awakenings increases. Using a longitudinal study design we are able to document these changes in individual Drosophila over the course of their lifespan. We have also found that an increase in oxidative stress produces changes in the sleep:wake cycle that are similar to those caused by changing;conversely, decreasing oxidative stress strengthens the cycle. We hypothesize that the deterioration of sleep:wake cycles contributes to the determination of lifespan and is caused, at least in part, by a buildup of oxidative damage. To address this hypothesis wewill: (i) Determine the relationship between sleep:wake cycle strength and lifespan. We will assay changes in sleep:wake cycles throughout life in flies with altered lifespan and test the hypothesis that these changes are associated with physiological, rather than chronological, age. (2) Examine oxidative stress as a possible mechanism for the age-related breakdown in sleep:wake cycles. We will determine how increased and decreased oxidative stress affect the changes that occur in sleep:wake cycles with age. We will also identify specific behavioral and molecular effects of oxidative stress on the sleep-regulating circadian and homeostatic systems and compare these with the effects of age. (3) Manipulate sleep and assay effects upon lifespan. We will alter environmental conditions or use genetic or pharmacological interventions to increase or decrease sleep consolidation, and assay effects upon lifespan. These experiments will indicate if sleep fragmentation contributes to the aging process. In the long-term, the knowledge gained from these studies should help to develop strategies for treating sleep problems in the elderly. Treatment ofthese problems may also alleviate other symptoms ofaging.
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