title: Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila.
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.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA. Electronic address: skatewa@buckinstitute.org.
authors.forename: Subhash D
authors.initials: SD
authors.lastname: Katewa
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Akagi
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Neelanjan
authors.initials: N
authors.lastname: Bose
authors.affiliation: Department of Integrative Biology, Oregon State University, 3029 Cordley Hall, Corvallis, OR 97331, USA.
authors.forename: Kuntol
authors.initials: K
authors.lastname: Rakshit
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Camarella
authors.affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hall
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Sonnet
authors.initials: S
authors.lastname: Davis
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Nelson
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Brem
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: Amita
authors.initials: A
authors.lastname: Sehgal
authors.affiliation: Department of Integrative Biology, Oregon State University, 3029 Cordley Hall, Corvallis, OR 97331, USA.
authors.forename: Jadwiga M
authors.initials: JM
authors.lastname: Giebultowicz
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA. Electronic address: pkapahi@buckinstitute.org.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kapahi
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D057906:Circadian Clocks; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008136:Longevity; D008297:Male; D015398:Signal Transduction
chemical_list: C120526:Clk protein, Drosophila; D029721:Drosophila Proteins; C096445:tim protein, Drosophila; D056926:CLOCK Proteins