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Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila
Open accessAbstract
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.
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“the ability of caloric restriction to extend Drosophila lifespan and improve fat metabolism depends on circadian regulation (Katewa et al., 2016).”
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Metadata
- Authors
- Katewa, S. D., Akagi, K., Bose, N., Rakshit, K., Camarella, T., Zheng, X., Hall, D., Davis, S., Nelson, C. S., Brem, R. B., Ramanathan, A., Sehgal, A., Giebultowicz, J. M., & Kapahi, P.
- Affiliations
- Buck Institute for Research on Aging (US)
- Oregon State University (US)
- University of Pennsylvania (US)
- Corresponding author
- Katewa, Subhash D.
- Kapahi, Pankaj
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 23
- Issue
- 1
- Pages
- 143-154
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4715572
- OpenAlex
- W2175005753
- Cited by
- 173
- References
- 78
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 14 · 2023: 20 · 2022: 12 · 2021: 18 · 2020: 17 · 2019: 14 · 2018: 18 · 2017: 23 · 2016: 13
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ellison Medical Foundation
- American Federation for Aging Research
- Larry L. Hillblom Foundation
- National Institutes of Health (AG038012, AG045835, R01 AG045830, R01AG038688)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Keywords
- circadian clock, dietary restriction, lifespan extension, TIMELESS, period, peripheral tissues, fat metabolism, lipid metabolism, medium-chain triglycerides, aging, Drosophila
- MeSH terms
- Animals, Drosophila melanogaster, Female, Gene Expression Regulation, Longevity, Male, Signal Transduction, Gene Expression, Drosophila Proteins, Caloric Restriction, Lipid Metabolism, CLOCK Proteins, Circadian Clocks
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