ArticlePLoS genetics2018
mTOR signaling regulates central and peripheral circadian clock function.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
107 citing papers in PubMed, 196 citations in OpenAlex.
- Sex-specific circadian and behavioral phenotypes in aged growth hormone receptor knockout mice.GeroScience · 2026Article
- Timing the strain: skeletal muscle clock as regulator of physical activity.npj metabolic health and disease · 2026Review
- Article
- mTOR signaling contributes to system-driven rhythmic gene expression in mouse liver.Science advances · 2026Article
- Divergent signaling profiles in mTOR gain-of-function Smith-Kingsmore syndrome (SKS) and TSC2 deficiency.bioRxiv : the preprint server for biology · 2026Article
- An unrecognized host response to microbial exposure resets circadian timing.bioRxiv : the preprint server for biology · 2026Article
- β-Hydroxybutyrate Modulates Metabolic Signaling and Partially Restores Peripheral Circadian Rhythms in High-Fat Diet-Fed Mice.Foods (Basel, Switzerland) · 2026Article
- Review
- The Influence of Acute Beta-Hydroxy Beta-Methylbutyrate (HMB) Ingestion on the Human Skeletal Muscle Transcriptome.Nutrients · 2026Article
- Hepatocellular Carcinoma Around the Clock.Current oncology (Toronto, Ont.) · 2026Review
- Running out the clock: Circadian rhythm dysfunction in cognitive disease.International review of neurobiology · 2026Review
- Effects of Chrono-Exercise and Chrono-Nutrition on Muscle Health: Understanding the Molecular Mechanisms Activated by Timed Exercise and Consumption of Proteins and Carbohydrates.Nutrition reviews · 2025Review
- Mechanistic insights into the interaction between epilepsy and sleep.Nature reviews. Neurology · 2025Review
- Review
- A Compensated Clock: Temperature and Nutritional Compensation Mechanisms Across Circadian Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Time Restricted Eating: A Valuable Alternative to Calorie Restriction for Addressing Obesity?Current obesity reports · 2025Review
- Developmental mechanisms underlying pediatric epilepsy.Frontiers in neurology · 2025Review
- Circadian clocks and adaptive immune function: from mechanisms to therapeutic applications.Frontiers in immunology · 2025Review
- Circadian system and aging: where both times interact.Frontiers in aging · 2025Review
- GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.American journal of physiology. Endocrinology and metabolism · 2024Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
The circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN). Given that mTOR activities exhibit robust circadian oscillations in a variety of tissues and cells including the SCN, here we continued to investigate the role of mTOR in orchestrating autonomous clock functions in central and peripheral circadian oscillators. Using a combination of genetic and pharmacological approaches we show that mTOR regulates intrinsic clock properties including period and amplitude. In peripheral clock models of hepatocytes and adipocytes, mTOR inhibition lengthens period and dampens amplitude, whereas mTOR activation shortens period and augments amplitude. Constitutive activation of mTOR in Tsc2-/-fibroblasts elevates levels of core clock proteins, including CRY1, BMAL1 and CLOCK. Serum stimulation induces CRY1 upregulation in fibroblasts in an mTOR-dependent but Bmal1- and Period-independent manner. Consistent with results from cellular clock models, mTOR perturbation also regulates period and amplitude in the ex vivo SCN and liver clocks. Further, mTOR heterozygous mice show lengthened circadian period of locomotor activity in both constant darkness and constant light. Together, these results support a significant role for mTOR in circadian timekeeping and in linking metabolic states to circadian clock functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.