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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
RETRACTED: LKB1 and AMPK maintain epithelial cell polarity under energetic stress
Mirouse, V., Swick, L. L., Kazgan, N., Johnston, D. S., & Brenman, J. E. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200702053 · Cited by 190
RetractedNIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107
Effects of intermittent fasting on health, aging, and disease
de Cabo, R., & Mattson, M. P. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1905136 · Cited by 1,605
Circadian physiology of metabolism
Panda, S. (2016) · Science · doi:10.1126/science.aah4967 · Cited by 1,092
Hughes, M. E., Hogenesch, J. B., & Kornacker, K. (2010) · Journal of Biological Rhythms · doi:10.1177/0748730410379711 · Cited by 1,087
Claesson, M. J., Wang, Q., O’Sullivan, Ó., Greene-Diniz, R., Cole, J. R., Ross, R. P., & O’Toole, P. W. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq873 · Cited by 1,016
Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan
Longo, V. D., & Panda, S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.001 · Cited by 1,013
Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body
Scott, R. C., Schuldiner, O., & Neufeld, T. P. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.07.009 · Cited by 979
Chaix, A., Zarrinpar, A., Miu, P., & Panda, S. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.11.001 · Cited by 956
Autophagy as a promoter of longevity: insights from model organisms
Hansen, M., Rubinsztein, D. C., & Walker, D. W. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0033-y · Cited by 754
Prandiology of Drosophila and the CAFE assay
Ja, W. W., Carvalho, G. B., Mak, E. M., de la Rosa, N. N., Fang, A. Y., Liong, J. C., Brummel, T., & Benzer, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702726104 · Cited by 717
Self-citationIndependent Photoreceptive Circadian Clocks Throughout Drosophila
Plautz, J. D., Kaneko, M. A. N., Hall, J. C., & Kay, S. A. (1997) · Science · doi:10.1126/science.278.5343.1632 · Cited by 640
Rera, M., Clark, R. I., & Walker, D. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215849110 · Cited by 619
Circadian clock genes and the transcriptional architecture of the clock mechanism
Cox, K. H., & Takahashi, J. S. (2019) · Journal of Molecular Endocrinology · doi:10.1530/jme-19-0153 · Cited by 514
Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog
Rera, M., Bahadorani, S., Cho, J., Koehler, C. L., Ulgherait, M., Hur, J. H., Ansari, W. S., Lo, T., Jones, D. L., & Walker, D. W. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.09.013 · Cited by 472
Self-citationCircadian Organization of Behavior and Physiology in Drosophila
Allada, R., & Chung, B. Y. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135815 · Cited by 456
Extension of Drosophila Life Span by RNAi of the Mitochondrial Respiratory Chain
Copeland, J. M., Cho, J., Lo, T., Hur, J. H., Bahadorani, S., Arabyan, T., Rabie, J., Soh, J., & Walker, D. W. (2009) · Current Biology · doi:10.1016/j.cub.2009.08.016 · Cited by 409
A Molecular Mechanism for Circadian Clock Negative Feedback
Duong, H. A., Robles, M. S., Knutti, D., & Weitz, C. J. (2011) · Science · doi:10.1126/science.1196766 · Cited by 375
Duffy, J. F., Zitting, K.-M., & Chinoy, E. D. (2015) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2015.08.002 · Cited by 367
Rana, A., Rera, M., & Walker, D. W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216197110 · Cited by 335
Circadian rhythms, time-restricted feeding, and healthy aging
Manoogian, E. N. C., & Panda, S. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.12.006 · Cited by 330
AMPK Modulates Tissue and Organismal Aging in a Non-Cell-Autonomous Manner
Ulgherait, M., Rana, A., Rera, M., Graniel, J. V., & Walker, D. W. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.006 · Cited by 320
Self-citationAgeing in Drosophila: The role of the insulin/Igf and TOR signalling network
Partridge, L., Alic, N., Bjedov, I., & Piper, M. D. W. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.09.003 · Cited by 313
Regulation of Feeding and Metabolism by Neuronal and Peripheral Clocks in Drosophila
Xu, K., Zheng, X., & Sehgal, A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.006 · Cited by 306
Time-restricted feeding attenuates age-related cardiac decline in Drosophila
Gill, S., Le, H. D., Melkani, G. C., & Panda, S. (2015) · Science · doi:10.1126/science.1256682 · Cited by 272
Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging
Chang, J. T., Kumsta, C., Hellman, A. B., Adams, L. M., & Hansen, M. (2017) · eLife · doi:10.7554/elife.18459 · Cited by 272
Making Time: Conservation of Biological Clocks from Fungi to Animals
Dunlap, J., & Loros, J. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0039-2016 · Cited by 163
Villanueva, J. E., Livelo, C., Trujillo, A. S., Chandran, S., Woodworth, B., Andrade, L., Le, H. D., Manor, U., Panda, S., & Melkani, G. C. (2019) · Nature Communications · doi:10.1038/s41467-019-10563-9 · Cited by 160
Catterson, J. H., Khericha, M., Dyson, M. C., Vincent, A. J., Callard, R., Haveron, S. M., Rajasingam, A., Ahmad, M., & Partridge, L. (2018) · Current Biology · doi:10.1016/j.cub.2018.04.015 · Cited by 152
Tricoire, H., Battisti, V., Trannoy, S., Lasbleiz, C., Pret, A., & Monnier, V. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.05.004 · Cited by 147
Kaneko, M. A. N., Park, J. H., Cheng, Y., Hardin, P. E., & Hall, J. C. (2000) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(20000605)43:3 · Cited by 138
Fasting Imparts a Switch to Alternative Daily Pathways in Liver and Muscle
Kinouchi, K., Magnan, C., Ceglia, N., Liu, Y., Cervantes, M., Pastore, N., Huynh, T., Ballabio, A., Baldi, P., Masri, S., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.077 · Cited by 135
Circadian autophagy rhythm: a link between clock and metabolism?
Ma, D., Li, S., Molusky, M. M., & Lin, J. D. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.03.004 · Cited by 106
Postprandial sleep mechanics in Drosophila
Murphy, K. R., Deshpande, S. A., Yurgel, M. E., Quinn, J. P., Weissbach, J. L., Keene, A. C., Dawson-Scully, K. D., Huber, R., Tomchik, S. M., & Ja, W. W. (2016) · eLife · doi:10.7554/elife.19334 · Cited by 105
Self-citationTime-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage
Wang, H., Spyk, E. N. V., Liu, Q., Geyfman, M., Salmans, M., Kumar, V., Ihler, A., Li, N., Takahashi, J. S., & D, B. A. M. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.022 · Cited by 105
Circadian regulation of mitochondrial uncoupling and lifespan
Ulgherait, M., Chen, A., McAllister, S. F., Kim, H. X., Delventhal, R., Wayne, C. R., Garcia, C., Recinos, Y., Oliva, M. K., Canman, J. C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15617-x · Cited by 91
Self-citationAltering Drosophila S6 kinase activity is consistent with a role for S6 kinase in growth
Barcelo, H., & Stewart, M. J. (2002) · Genesis · doi:10.1002/gene.10132 · Cited by 78
Delventhal, R., Pantalia, M., O'Connor, R. M., Ulgherait, M., Kim, H. X., Basturk, M. K., Canman, J. C., & Shirasu‐Hiza, M. (2019) · eLife · doi:10.7554/elife.48308 · Cited by 64
Self-citationCrosstalk of clock gene expression and autophagy in aging
Kalfalah, F. M., Janke, L., Schiavi, A., Tigges, J., Ix, A., Ventura, N., Boege, F., & Reinke, H. (2016) · Aging · doi:10.18632/aging.101018 · Cited by 56
Simultaneous measurement of sleep and feeding in individual Drosophila
Murphy, K. R., Park, S. J., Huber, R., & Ja, W. W. (2017) · Nature Protocols · doi:10.1038/nprot.2017.096 · Cited by 53
Self-citationYamamuro, D., Takahashi, M., Nagashima, S., Wakabayashi, T., Yamazaki, H., Takei, A., Takei, S., Sakai, K., Ebihara, K., Iwasaki, Y., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0234439 · Cited by 47
García-Gaytán, A. C., Miranda‐Anaya, M., Turrubiate, I., Portugal, L. L.-D., Bocanegra-Botello, G. N., López-Islas, A., Díaz‐Muñoz, M., & Méndez, I. G. (2020) · Scientific Reports · doi:10.1038/s41598-020-66538-0 · Cited by 30
Dietary Restriction Extends the Lifespan of Circadian Mutants tim and per
Ulgherait, M., Chen, A., Oliva, M. K., Kim, H. X., Canman, J. C., Ja, W. W., & Shirasu‐Hiza, M. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.11.002 · Cited by 23
Self-citationMonitoring Autophagy in Drosophila Using Fluorescent Reporters in the UAS-GAL4 SystemPreprint
DeVorkin, L., & Gorski, S. M. (2014) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot080341 · Cited by 22
Time-restricted feeding prolongs lifespan in Drosophila in a peripheral clock-dependent mannerPreprint
Cabrera, D., Young, M. W., & Axelrod, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.14.296368 · Cited by 8
Research works printed but not linked: 1
- Delventhal, R. et al. Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption. eLife 8, e48308 (2019). · DOI
Cited by
Sorted by citations
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
