Caloric restriction effects on liver mTOR signaling are time-of-day dependent
Open accessAbstract
The regulation of mechanistic target of rapamycin (mTOR) signaling contributes to the metabolic effects of a calorie restriction (CR) diet. We assayed the effect of CR on the activity of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) in the liver of mice at six different times across the day. CR effects on mTORC1 and mTORC2 activities were time-of-day dependent. CR induced mTORC1 activity at one time, reduced at two times and has no effect during other times. CR induced mTORC2 activity at one time of the day and has no effects at other times. Circadian clocks are implemented in the regulation of mTOR signaling in mammals and mechanisms of CR. We assayed the effect of CR on mTOR signaling in the liver of mice deficient for circadian transcriptional regulators BMAL1 and CRYs. The CR induced suppression of mTORC1 activity was observed in both clock mutants, while up regulation of mTORC2 was observed in the liver of CRY deficient but not in the liver of BMAL1 deficient mice. Our finding revealed that CR has different time dependent effect on the activity of mTOR complexes 1 and 2 and suggest that circadian clock protein BMAL1 is involved in the up regulation of mTORC2 upon CR in mammals.
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Fasting is thought to work at least in part through the inhibition of insulin/IGF-1/mTORC1 signaling.
“On the molecular level, fasting is not well understood but based on the data from studies on fasting-mediated longevity and stress resistance, it is thought to work at least in part through the inhibition of insulin/IGF-1/mTORC1 signaling15–18.”
From RETRACTED ARTICLE: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression (2020) · cites this paper as [17]
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References 38 · Cited by 36
- Authors
- Tulsian, R., Velingkaar, N., & Kondratov, R.
- Affiliations
- Cleveland State University (US)
- Corresponding author
- Kondratov, Roman
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2018-07-16
- Volume
- 10
- Issue
- 7
- Pages
- 1640-1648
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC6075448
- OpenAlex
- W2884013871
- Cited by
- 36
- References
- 38
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 4
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EngagedScholarship @ Cleveland State University (Cleveland State University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (1s10od025252-01)
- National Institute on Aging (R01AG039547)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- caloric restriction, mTOR signaling, mTORC1, mTORC2, liver, circadian clock, time-of-day dependence, Bmal1, crying, clock mutants
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Liver, Signal Transduction, Mice, Knockout, Caloric Restriction, Mice, ARNTL Transcription Factors, Cryptochromes, TOR Serine-Threonine Kinases
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