Article thumbnail

Loss of circadian clock accelerates aging in neurodegeneration-prone mutants



This is the authors' peer reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found here: COVERAGE: A news release based on this journal publication, which is written for a lay audience and has been approved by an author of the study, is available online: clocks generate rhythms in molecular, cellular, physiological, and behavioral\ud processes. Recent studies suggest that disruption of the clock mechanism accelerates organismal\ud senescence and age-related pathologies in mammals. Impaired circadian rhythms are observed in\ud many neurological diseases; however, it is not clear whether loss of rhythms is the cause or result\ud of neurodegeneration, or both. To address this important question, we examined the effects of\ud circadian disruption in Drosophila melanogaster mutants that display clock-unrelated\ud neurodegenerative phenotypes. We combined a null mutation in the clock gene period (per⁰¹)\ud that abolishes circadian rhythms, with a hypomorphic mutation in the carbonyl reductase gene\ud sniffer (sni¹), which displays oxidative stress induced neurodegeneration. We report that\ud disruption of circadian rhythms in sni¹ mutants significantly reduces their lifespan compared to\ud single mutants. Shortened lifespan in double mutants was coupled with accelerated neuronal\ud degeneration evidenced by vacuolization in the adult brain. In addition, per⁰¹ sni¹ flies showed\ud drastically impaired vertical mobility and increased accumulation of carbonylated proteins\ud compared to age-matched single mutant flies. Loss of per function does not affect sni mRNA\ud expression, suggesting that these genes act via independent pathways producing additive effects.\ud Finally, we show that per⁰¹ mutation accelerates the onset of brain pathologies when combined\ud with neurodegeneration-prone mutation in another gene, swiss cheese (sws¹), which does not\ud operate through the oxidative stress pathway. Taken together, our data suggest that the period\ud gene may be causally involved in neuroprotective pathways in aging Drosophila

Topics: biological clock, circadian rhythms, neuronal health, protein carbonyls, RING assay
Publisher: Elsevier
Year: 2011
DOI identifier: 10.1016/j.nbd.2011.12.034
OAI identifier:
Provided by: ScholarsArchive@OSU
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • (external link)
  • (external link)
  • http://www.journals.elsevier.c... (external link)
  • Suggested articles

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.