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Cell Metab. 2016 Jan 12;23(1):143-54. doi: 10.1016/j.cmet.2015.10.014. Epub 2015 Nov 25.

Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila.

Author information

1
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA. Electronic address: skatewa@buckinstitute.org.
2
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
3
Department of Integrative Biology, Oregon State University, 3029 Cordley Hall, Corvallis, OR 97331, USA.
4
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.
5
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA. Electronic address: pkapahi@buckinstitute.org.

Abstract

Endogenous circadian clocks orchestrate several metabolic and signaling pathways that are known to modulate lifespan, suggesting clocks as potential targets for manipulation of metabolism and lifespan. We report here that the core circadian clock genes, timeless (tim) and period (per), are required for the metabolic and lifespan responses to DR in Drosophila. Consistent with the involvement of a circadian mechanism, DR enhances the amplitude of cycling of most circadian clock genes, including tim, in peripheral tissues. Mass-spectrometry-based lipidomic analysis suggests a role of tim in cycling of specific medium chain triglycerides under DR. Furthermore, overexpression of tim in peripheral tissues improves its oscillatory amplitude and extends lifespan under ad libitum conditions. Importantly, effects of tim on lifespan appear to be mediated through enhanced fat turnover. These findings identify a critical role for specific clock genes in modulating the effects of nutrient manipulation on fat metabolism and aging.

PMID:
26626459
PMCID:
PMC4715572
DOI:
10.1016/j.cmet.2015.10.014
[Indexed for MEDLINE]
Free PMC Article

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