Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice

Science, Journal Year: 2022, Volume and Issue: 376(6598), P. 1192 - 1202

Published: May 5, 2022

Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising question if is calories, or time day that cause this increased span. We show here 30% CR was sufficient to extend span 10%; however, a daily fasting interval circadian alignment acted together 35% in male C57BL/6J mice. These effects were independent body weight. Aging induced widespread increases gene expression associated with inflammation decreases genes encoding components metabolic pathways liver from ad libitum-fed at night ameliorated these aging-related changes. Our results interventions promote longevity provide perspective further explore aging.

Language: Английский

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Circadian rhythms and disorders of the timing of sleep

The Lancet, Journal Year: 2022, Volume and Issue: 400(10357), P. 1061 - 1078

Published: Sept. 1, 2022

Language: Английский

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Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(3)

Published: Jan. 15, 2021

The circadian clock and feeding rhythms are both important regulators of rhythmic gene expression in the liver. To further dissect respective contributions clock, we analyzed differential rhythmicity liver tissue samples across several conditions. We developed a statistical method tailored to compare messenger RNA (mRNA) mouse knockout models multiple genes, as well PARbZip output transcription factors (Hlf/Dbp/Tef). Mice were exposed ad libitum or night-restricted under regular light-dark cycles. During feeding, genetic ablation core attenuated rhythmic-feeding patterns, which could be restored by regimen. High-amplitude mRNA wild-type livers driven but also contributed expression, albeit with significantly lower amplitudes. observed that Bmal1 Cry1/2 knockouts differed their residual expression. Differences mean levels between wild types correlated type. Surprisingly, mice, targets more strongly impacted than rhythms, potentially due activity D-box-repressor NFIL3. Genes lost identified indirect targets. Our findings provide insights into diurnal transcriptome regulators. In addition, gained on specific effects feeding-fasting cycle.

Language: Английский

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Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: July 20, 2021

Branched-chain amino acids (BCAAs) are critical for skeletal muscle and whole-body anabolism energy homeostasis. They also serve as signaling molecules, example, being able to activate mammalian/mechanistic target of rapamycin complex 1 (mTORC1). This has implication macronutrient metabolism. However, elevated circulating levels BCAAs their ketoacids well impaired catabolism these (AAs) implicated in the development insulin resistance its sequelae, including type 2 diabetes, cardiovascular disease, some cancers, although other studies indicate supplements AAs may help management chronic diseases. Here, we first reviewed especially this tissue contributes most whole body disposal BCAA. We then emerging mechanisms control enzymes involved regulating BCAA catabolism. Such include regulation abundance by microRNA post translational modifications such phosphorylation, acetylation, ubiquitination. implications metabolism comment on outstanding questions AAs, post-transcriptional/post-translational modification that regulate catabolism, impact circadian rhythm, age mTORC1 enzymes. Answers facilitate emergence treatment/management options can patients suffering from diseases linked BCAAs.

Language: Английский

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Genetics of circadian rhythms and sleep in human health and disease

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(1), P. 4 - 20

Published: Aug. 26, 2022

Language: Английский

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Gut microbiota as a transducer of dietary cues to regulate host circadian rhythms and metabolism

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(10), P. 679 - 689

Published: May 17, 2021

Language: Английский

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Top Priorities for Cerebroprotective Studies—A Paradigm Shift: Report From STAIR XI

Stroke, Journal Year: 2021, Volume and Issue: 52(9), P. 3063 - 3071

Published: July 22, 2021

Despite years of basic research and pioneering clinical work, ischemic stroke remains a major public health concern. Prior STAIR (Stroke Treatment Academic Industry Roundtable) conferences identified both failures trial design in preclinical assessment developing putative treatments. At XI, participants workshop no. 1 Top Priorities for Neuroprotection sought to redefine the neuroprotection paradigm given paucity evidence underlying assessment, offer consensus-based recommendations. proposes term brain cytoprotection or cerebroprotection replace when intention an investigation is demonstrate that new, candidate treatment benefits entire brain. Although “time still brain,” tissue imaging techniques have been developed identify patients with predicted core injury penumbral, salvageable tissue, regardless time after symptom onset. XI called this approach window select recanalization. Elements neurovascular unit show differential vulnerability evolving over differing scales different regions. target suggest therapies elements at times. Based on contemporary principles rigor transparency, updated, revised, enhanced recommendations new treatments 2 phases: exploratory qualification phase definitive validation phase. For treatments, investigators should carefully characterize mechanism action, pharmacokinetics/pharmacodynamics, engagement, confirm penetration through blood-brain barrier. Before trials, testing molecules models could proceed comprehensive manner using animals sexes include significant variables such as age comorbid conditions. Comprehensive might multicenter, collaborative testing, example, network trials. In absence proven cerebroprotective agent use gold standard, however, it speculative whether can effectively predict outcome.

Language: Английский

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Dietary regulation in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 23, 2022

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan delaying ageing various species such as yeast, drosophila, rodent, primate human. It emerges develop precision-nutrition therapeutics slow age-related biological processes treat diverse diseases. However, nutritive advantages frequently diversify among individuals well organs tissues, which brings challenges this field. In review, we summarize different forms of dietary interventions extensively prescribed improvement disease treatment pre-clinical or clinical. We discuss nutrient-mediated mechanisms including metabolic regulators, metabolism pathways, epigenetic circadian clocks. Comparably, describe diet-responsive effectors by influence endocrinic, immunological, microbial neural states responsible improving health preventing multiple diseases humans. Furthermore, expatiate patterns dietotheroapies, fasting, calorie-restricted diet, ketogenic high-fibre plants-based protein restriction diet with specific reduction amino acids microelements, potentially affecting morbid states. Altogether, emphasize profound nutritional therapy, highlight crosstalk explored critical factors individualized therapeutic approaches predictors.

Language: Английский

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Circadian rhythms and cancers: the intrinsic links and therapeutic potentials

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 4, 2022

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting and activity-rest coordinating the behavior physiology all organs for whole-body homeostasis. Acute disruption may lead to transient discomfort, whereas long-term irregular will result in dysfunction organism, therefore increasing risks numerous diseases especially cancers. Indeed, both epidemiological experimental evidence has demonstrated intrinsic link between dysregulated cancer. Accordingly, rapidly understanding molecular mechanisms rhythms opening new options cancer therapy, possibly by modulating clock. In this review, we first describe general regulators their functions on addition, provide insights into underlying how several types (including sleep-wake, eating-fasting, activity-rest) can drive progression, which expand our development from clock perspective. Moreover, also summarize potential applications treatment, optional therapeutic strategy patients.

Language: Английский

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Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3392 - 3392

Published: Feb. 8, 2023

Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce production, expanding social life around the clock. However, physiology behavior that evolved in context 24 h solar days are frequently perturbed by exposure to at night. This is particularly salient circadian rhythms, result endogenous biological clocks with a rhythm ~24 h. Circadian rhythms govern features behavior, set precisely primarily during day, though other factors, such as timing meals, can also affect rhythms. significantly affected night shift work because nocturnal light, electronic devices, shifts meals. Night workers increased risk for metabolic disorder, well several types cancer. Others who exposed or late mealtimes show disrupted cardiac disorders. It imperative understand how alter function develop strategies mitigate their negative effects. In this review, we provide an introduction physiological regulation homeostasis suprachiasmatic nucleus (SCN), SCN-mediated hormones display including melatonin glucocorticoids. Next, discuss circadian-gated processes sleep food intake, followed modern lighting disrupts molecular clock Lastly, identify disruptions metabolism increase susceptibility syndrome cardiovascular diseases, various harmful consequences associated on health.

Language: Английский

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