The Circadian System and Aging of Drosophila
Circadian clocks generate daily rhythms in gene expression, cellular functions, physiological processes and behavior. The core clock mechanism is cell-autonomous and consists of molecular negative feedback loops that turn over with an endogenous circa 24 h period. While daily oscillations in the activity of clock genes and proteins are well understood in young fruit flies Drosophila melanogaster, much less is known about how the clock mechanism changes during organismal aging. Emerging data suggest that aging is associated with reduced expression of some core clock genes in peripheral head clocks, while a similar reduction may not occur in central clock neurons regulating behavioral rhythms. Clock-controlled processes also change with age. Similar as in humans, rest/activity rhythms tend to weaken with age in fruit flies, suggesting conservation of aging-related circadian impairments. The importance of circadian clocks for healthy aging is supported by observations that their genetic or environmental disruption is associated with reduced healthspan and lifespan . For example, arrhythmia caused by mutations in core clock genes lead to symptoms of accelerated aging in both flies and mammals, including neurodegenerative phenotypes. Despite the wealth of descriptive data, the mechanisms by which functional clocks confer healthspan and lifespan benefits are poorly understood. Recent studies in Drosophila discussed here are beginning to unravel causative relationships between circadian system and aging. They also suggest that clocks may be involved in inducing rhythmic expression of specific genes late in life in response to age-related increase in oxidative stress. The goal of this chapter is to summarize modest insights that were so far made into links between circadian system and aging and to illuminate the power of Drosophila for future mechanistic research in this important area.
KeywordsClock genes Clock-controlled genes Genome-wide gene expression Lifespan Healthspan Neurodegeneration
The author thanks Eileen Chow for help with figures and reading of the manuscript as well as Dani Long for reading of the manuscript. Author’s research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R01 AG045830 and R21AG052950 to JMG.
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