The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Circadian autophagy drives iTRF-mediated longevity
Open accessAbstract
Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans 1-5. TRF restricts food intake to specific hours of the day. Because TRF controls the timing of feeding, rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions; the underlying molecular mechanisms of its effects remain unclear. Here, to exploit the genetic tools and well-characterized ageing markers of Drosophila, we developed an intermittent TRF (iTRF) dietary regimen that robustly extended fly lifespan and delayed the onset of ageing markers in the muscles and gut. We found that iTRF enhanced circadian-regulated transcription and that iTRF-mediated lifespan extension required both circadian regulation and autophagy, a conserved longevity pathway. Night-specific induction of autophagy was both necessary and sufficient to extend lifespan on an ad libitum diet and also prevented further iTRF-mediated lifespan extension. By contrast, day-specific induction of autophagy did not extend lifespan. Thus, these results identify circadian-regulated autophagy as a critical contributor to iTRF-mediated health benefits in Drosophila. Because both circadian regulation and autophagy are highly conserved processes in human ageing, this work highlights the possibility that behavioural or pharmaceutical interventions that stimulate circadian-regulated autophagy might provide people with similar health benefits, such as delayed ageing and lifespan extension.
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“Time-restricted feeding (TRF), a healthy diet, extends the Drosophila lifespan and delays the onset of ageing markers in the muscles and gut by stimulating circadian-regulated autophagy.487”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [487]
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“Life time extension of a similar intermittent fasting regimen in flies has been attributed to the nighttime-specific upregulation of autophagy-stimulatory genes 155 , but this has not yet been investigated in mammals.”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [155]
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1 retracted
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RetractedNIH Image to ImageJ: 25 years of image analysis
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Hallmarks of aging: An expanding universe
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023) · Cell · doi:10.1016/j.cell.2022.11.001 · Cited by 6,549
Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice
Acosta-Rodríguez, V., Rijo-Ferreira, F., Izumo, M., Xu, P., Wight-Carter, M., Green, C. B., & Takahashi, J. S. (2022) · Science · doi:10.1126/science.abk0297 · Cited by 390
Nutrition, longevity and disease: From molecular mechanisms to interventions
Longo, V. D., & Anderson, R. M. (2022) · Cell · doi:10.1016/j.cell.2022.04.002 · Cited by 345
Dietary regulation in health and disease
Wu, Q., Gao, Z., Yu, X., & Wang, P. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01104-w · Cited by 190
Spermidine is essential for fasting-mediated autophagy and longevity
Hofer, S. J., Daskalaki, I., Bergmann, M., Friščić, J., Zimmermann, A., Mueller, M. I., Abdellatif, M., Nicastro, R., Masser, S., Durand, S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01468-x · Cited by 186
Metadata
- Authors
- Ulgherait, M., Midoun, A. M., Park, S. J., Gatto, J. A., Tener, S. J., Siewert, J., Klickstein, N., Canman, J. C., Ja, W. W., & Shirasu-Hiza, M.
- Affiliations
- Columbia University (US)
- Université Paris Sciences et Lettres (FR)
- Scripps Research Institute (US)
- ORCID
- Venue
- Nature
- Published
- 2021-09-29
- Volume
- 598
- Issue
- 7880
- Pages
- 353-358
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9395244
- OpenAlex
- W3202239352
- Cited by
- 226
- References
- 46
- Citations by year
- 2026: 30 · 2025: 48 · 2024: 44 · 2023: 56 · 2022: 43 · 2021: 5
- FWCI
- 13.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (1r56ag065986-01, P40OD018537)
- National Institute on Aging (R56AG065986, R01AG045842)
- National Institute of General Medical Sciences (R01GM117407, T32GM007088, R01GM105775, R35GM127049, T32GM141882, R01GM130764)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- circadian rhythm, autophagy, lifespan extension, aging, Drosophila, feeding timing, muscle aging, ad libitum feeding
- MeSH terms
- Aging, Animals, Autophagy, Circadian Rhythm, Darkness, Drosophila melanogaster, Feeding Behavior, Female, Longevity, Male, Time Factors, Biomarkers, Circadian Clocks
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