RESEARCH PAPER


The circadian clock gene period extends healthspan in aging Drosophila melanogaster

Natraj Krishnan1, Doris Kretzschmar2, Kuntol Rakshit1, Eileen Chow1, Jadwiga M. Giebultowicz1
1 Department of Zoology, Oregon State University , Corvallis, OR 97331 USA
2 CROET- Oregon Health and Science University, Portland, OR 97239 USA
Running title:
Circadian clock delays aging in fly
Key words:
oxidative stress, longevity, RING, neurodegeneration, oxidative stress
Abbreviations:
PC: protein carbonyls, HNE: 4-hydroxynonenal, ROS: reactive oxygen species, RING: rapid iterative negative geotaxis
Received:
11/03/09; accepted: 11/18/09; published on line: 11/19/09
Correspondence:
E-mail:

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 (per01) 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 per01 but not in control flies. This homeostatic challenge also led to significantly higher accumulation of oxidative damage in per01 flies compared to controls. In addition, aging per01 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.