Authors: Krishnan N; Kretzschmar D; Rakshit K; Chow E; Giebultowicz JM
Abstract: There is increasing evidence that aging is affected by biological (circadian) clocks - the internal mechanisms that coordinate daily changes in gene expression, physiological functions and behavior with external day/night cycles. Recent data suggest that disruption of the mammalian circadian clock results in accelerated aging and increased age-related pathologies such as cancer; however, the links between loss of daily rhythms and aging are not understood. We sought to determine whether disruption of the circadian clock affects lifespan and healthspan in the model organism Drosophila melanogaster. We examined effects of a null mutation in the circadian clock gene period (per(01)) on the fly healthspan by challenging aging flies with short-term oxidative stress (24h hyperoxia) and investigating their response in terms of mortality hazard, levels of oxidative damage, and functional senescence. Exposure to 24h hyperoxia during middle age significantly shortened the life expectancy in per(01) but not in control flies. This homeostatic challenge also led to significantly higher accumulation of oxidative damage in per(01) flies compared to controls. In addition, aging per(01) flies showed accelerated functional decline, such as lower climbing ability and increased neuronal degeneration compared to age-matched controls. Together, these data suggest that impaired stress defense pathways may contribute to accelerated aging in the per mutant. In addition, we show that the expression of per gene declines in old wild type flies, suggesting that the circadian regulatory network becomes impaired with age.
Keywords: Aging/*genetics/physiology; Animals; Behavior, Animal/physiology; Circadian Rhythm/*genetics/physiology; Drosophila melanogaster/*genetics/physiology; Female; Gene Expression Regulation; Homeostasis/physiology; Hyperoxia/physiopathology; Longevity/*genetics/physiology; Male; Models, Animal; Mutation/genetics; Nerve Degeneration/physiopathology; Oxidative Stress/physiology; Period Circadian Proteins/*genetics/physiology|
Journal: Aging Volume: 1 Issue: 11 Pages: 937-48 Date: Feb. 17, 2010 PMID: 20157575 |
Krishnan N, Kretzschmar D, Rakshit K, Chow E, Giebultowicz JM (2009) The circadian clock gene period extends healthspan in aging Drosophila melanogaster. Aging 1: 937-48.
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