Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan
Open accessAbstract
Most animals alternate periods of feeding with periods of fasting often coinciding with sleep. Upon >24 hr of fasting, humans, rodents, and other mammals enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from the prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which food consumption is restricted to certain hours of the day, allows the daily fasting period to last >12 hr, thus imparting pleiotropic benefits. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting-mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMDs, both basic science and translational research are warranted to develop fasting-associated interventions into feasible, effective, and inexpensive treatments with the potential to improve healthspan.
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Metabolic switching promotes the release and utilization of fatty acids and ketone bodies-signaling molecules that may regulate diverse cellular pathways, enhance stress resistance, improve organ function, and protect against metabolic and inflammatory diseases.
“This metabolic switching promotes the release and utilization of fatty acids and ketone bodies—signaling molecules that may regulate diverse cellular pathways, enhance stress resistance, improve organ function, and protect against metabolic and inflammatory diseases (12, 44, 45).”
From Intermittent fasting versus continuous energy restriction in MASLD: a systematic review and meta-analysis (2026) · cites this paper as [45]
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Experimental — accuracy not yet measuredSecretion of signaling molecules produced by metabolic organs varies according to metabolic status, responding to fasting/feeding cycles, circadian rhythm, cold exposure, and exercise.
“The secretion of these signaling molecules varies according to the metabolic status of the body. They respond for instance to fasting and feeding cycles 14, to the circadian rhythm 15, to cold exposure 16, and to exercise17, thus participating in the organism's adaptive response and ensuring metabolic flexibility.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [14]
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- Authors
- Longo, V. D., & Panda, S.
- Affiliations
- University of Southern California (US)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Longo, Valter D.
- Panda, Satchidananda
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 23
- Issue
- 6
- Pages
- 1048-1059
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5388543
- OpenAlex
- W2440558121
- Cited by
- 1,013
- References
- 83
- Citations by year
- 2026: 120 · 2025: 143 · 2024: 107 · 2023: 102 · 2022: 111 · 2021: 142 · 2020: 107 · 2019: 63 · 2018: 63 · 2017: 43 · 2016: 11
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P01AG034906, R01AG020642)
- National Eye Institute (R01EY016807)
- National Cancer Institute (P30CA014195)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- fasting, circadian rhythm, time-restricted feeding, intermittent fasting, fasting-mimicking diet, healthspan, ketone bodies, glucose metabolism, metabolic switch, disease prevention, disease treatment
- MeSH terms
- Animals, Circadian Rhythm, Diet, Eating, Fasting, Feeding Behavior, Glucose, Humans, Ketones, Mammals, Mice
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