Cited by 227Genetics, Aging, and Longevity in Model OrganismsDietary Effects on HealthCircadian rhythm and melatonin

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Circadian autophagy drives iTRF-mediated longevity

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Ulgherait, Matt, Midoun, Adil M., Park, Scarlet J., Gatto, Jared A., Tener, Samantha J., Siewert, Julia, Klickstein, Naomi, Canman, Julie C., Ja, William W., Shirasu-Hiza, Mimi·2021·Nature

DOI 10.1038/s41586-021-03934-0PMC PMC9395244

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Abstract

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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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: Midoun, Adil M.
Park, Scarlet J.
Gatto, Jared A.
Tener, Samantha J.
Klickstein, Naomi
Canman, Julie C.
Ja, William W.
Shirasu-Hiza, Mimi
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2021-09-29
Volume: 598
Issue: 7880
Pages: 353-358
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-021-03934-0
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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