Effects of Aging on the Molecular Circadian Oscillations in Drosophila Public Deposited

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This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Informa Healthcare USA, Inc. and can be found at:  http://informahealthcare.com/cbi.

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  • Circadian clocks maintain temporal homeostasis by generating daily output rhythms in molecular, cellular, and physiological functions. Output rhythms, such as sleep/wake cycles and hormonal fluctuations, tend to deteriorate during aging in humans, rodents, and fruit flies. However, it is not clear whether this decay is caused by defects in the core transcriptional clock, or weakening of the clock-output pathways, or both. The authors monitored age-related changes in behavioral and molecular rhythms in Drosophila melanogaster. Aging was associated with disrupted rest/activity patterns and lengthening of the free-running period of the circadian locomotor activity rhythm. The expression of core clock genes was measured in heads and bodies of young, middle-aged, and old flies. Transcriptional oscillations of four clock genes, period, timeless, Par domain protein 1ϵ, and vrille, were significantly reduced in heads, but not in bodies, of aging flies. It was determined that reduced transcription of these genes was not caused by the deficient expression of their activators, encoded by Clock and cycle genes. Interestingly, transcriptional activation by CLOCK-CYCLE complexes was impaired despite reduced levels of the PERIOD repressor protein in old flies. These data suggest that aging alters the properties of the core transcriptional clock in flies such that both the positive and the negative limbs of the clock are attenuated.
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  • Rakshit, K., Krishnan, N., Guzik, E., Pyza, E., & Giebultowicz, J. (2012). Effects of aging on the molecular circadian oscillations in drosophila. CHRONOBIOLOGY INTERNATIONAL, 29(1), 5-14. doi: 10.3109/07420528.2011.635237
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