Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging

Sato, Shogo; Solanas, Guiomar; Peixoto, Francisca Oliveira; Bee, Leonardo; Symeonidi, Aikaterini; Schmidt, Mark S.; Brenner, Charles; Masri, Selma; Benitah, Salvador Aznar; Sassone–Corsi, Paolo

doi:10.1016/j.cell.2017.07.042

Cited by 297 publications

(320 citation statements)

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“…Calorie restriction (CR) delays aging and increases longevity in a variety of organisms (11,12) and affects circadian clocks. CR changes circadian rhythms in behavior and gene expression, thus regulating both central and peripheral circadian clocks, and the effect is conserved between flies and rodents (13)(14)(15)(16)(17). Circadian clocks are master regulators of metabolism (18), and it was speculated that at least some of the beneficial outcomes of CR are due to the effect on the clock (2,3).…”

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confidence: 99%

“…Circadian clocks are master regulators of metabolism (18), and it was speculated that at least some of the beneficial outcomes of CR are due to the effect on the clock (2,3). Recent analysis of circadian rhythms of mRNA abundance in the liver and skeletal muscles of young and old mice fed ad libitum (AL) or CR diets identifies a significant reprogramming of the circadian transcriptome by aging and CR (16,19), supporting the importance of the interaction between biologic clocks, diet, and aging.…”

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Calorie restriction reprograms diurnal rhythms in protein translation to regulate metabolism

et al. 2018

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Calorie restriction (CR) delays aging and affects the circadian clocks by reprogramming circadian rhythms in gene expression. To expand on the circadian mechanisms in CR, we assayed rhythms in the protein translation by analyzing polysome‐associated mRNAs in the liver of mice fed ad libitum (AL) and CR diets. Global comparison of the diets revealed that <1% of transcripts were differentially abundant in the polysomes. In contrast, the large differential, up to 10%, was detected when CR and AL diets were compared at individual times throughout the day. Most transcripts that were rhythmic under AL lost their rhythms, and many new transcripts gained rhythms under CR. Only a small fraction of transcripts, including the circadian clock genes, were rhythmic under both diets. Thus, CR strongly reprograms translation. CR affected translation of enzymes regulating long‐chain acetyl‐coenzyme A (Acyl‐CoA) metabolism. The expression of the Acyl‐CoA thioesterase (ACOT) family was induced upon CR, leading to the increased transcriptional activity of peroxisome proliferator‐activated receptor α, the transcriptional factor regulated by the ACOT products. We propose that the differential translation induced by CR leads to a temporal partition and reprogramming of metabolic processes and provides a link between CR, lipid metabolism, and the circadian clock.—Makwana, K., Gosai, N., Poe, A., Kondratov, R. V. Calorie restriction reprograms diurnal rhythms in protein translation to regulate metabolism. FASEB J. 33, 4473–4489 (2019). http://www.fasebj.org

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confidence: 99%

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Calorie restriction reprograms diurnal rhythms in protein translation to regulate metabolism

et al. 2018

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“…Other examples further demonstrate that liver circadian rhythms can be affected by extrinsic factors. When comparing young versus old mice, Sato et al () observed age induced reprogramming of the circadian hepatic transcript and chromatin landscapes. However, caloric restriction, which has been associated with clock re‐setting (Guan et al, ), counteracted age‐dependent changes (S. Sato et al, ).…”

Section: Liver Enhancer Dynamicsmentioning

confidence: 99%

“…When comparing young versus old mice, Sato et al () observed age induced reprogramming of the circadian hepatic transcript and chromatin landscapes. However, caloric restriction, which has been associated with clock re‐setting (Guan et al, ), counteracted age‐dependent changes (S. Sato et al, ). Earlier work has also established the role of body temperature as a universal cue in mammalian circadian transcriptional regulation (Buhr, Yoo, & Takahashi, ).…”

Section: Liver Enhancer Dynamicsmentioning

confidence: 99%

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

Cebola

2020

WIREs Mechanisms of Disease

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Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) result from complex interactions between intrinsic and extrinsic factors, including genetics and exposure to obesogenic environments. These risk factors converge in aberrant gene expression patterns in the liver, which are underlined by altered cis‐regulatory networks. In homeostasis and in disease states, liver cis‐regulatory networks are established by coordinated action of liver‐enriched transcription factors (TFs), which define enhancer landscapes, activating broad gene programs with spatiotemporal resolution. Recent advances in DNA sequencing have dramatically expanded our ability to map active transcripts, enhancers and TF cistromes, and to define the 3D chromatin topology that contains these elements. Deployment of these technologies has allowed investigation of the molecular processes that regulate liver development and metabolic homeostasis. Moreover, genomic studies of NAFLD patients and NAFLD models have demonstrated that the liver undergoes pervasive regulatory rewiring in NAFLD, which is reflected by aberrant gene expression profiles. We have therefore achieved an unprecedented level of detail in the understanding of liver cis‐regulatory networks, particularly in physiological conditions. Future studies should aim to map active regulatory elements with added levels of resolution, addressing how the chromatin landscapes of different cell lineages contribute to and are altered in NAFLD and NAFLD‐associated metabolic states. Such efforts would provide additional clues into the molecular factors that trigger this disease. This article is categorized under: Biological Mechanisms > Metabolism Biological Mechanisms > Regulatory Biology Laboratory Methods and Technologies > Genetic/Genomic Methods

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“…Yet, SIRT1 may be beneficial under specific circumstances to regulate circadian rhythm gene expression that can foster hepatocellular proliferation and liver regeneration following liver resection (156). More recent work also suggests an important role for SIRT1 targets with aging and circadian gene expression in the liver (157). …”

Section: Circadian Clock Genesmentioning

confidence: 99%

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Maiese¹

2018

CNR

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BACKGROUND With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs). RESULTS Circadian clock genes, non-coding RNAs, and FoxOs offer exciting prospects to potentially limit or remove the significant disability and death associated with neurodegenerative disorders. Each of these pathways have an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease such as atherosclerosis. FoxOs provide exciting prospects to block neuronal apoptotic death and to activate pathways of autophagy to remove toxic accumulations in neurons that can lead to neurodegenerative disorders. CONCLUSIONS Continued work with circadian clock genes, non-coding RNAs, and FoxOs can offer new prospects and hope for the development of vital strategies for the treatment of neurodegenerative diseases. These innovative investigative avenues have the potential to significantly limit disability and death from these devastating disorders.

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Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging

Cited by 297 publications

References 75 publications

Calorie restriction reprograms diurnal rhythms in protein translation to regulate metabolism

Calorie restriction reprograms diurnal rhythms in protein translation to regulate metabolism

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

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