Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress

Solanas, Guiomar; Peixoto, Francisca Oliveira; Perdiguero, Eusebio; Jardı́, Mercè; Ruiz‐Bonilla, Vanessa; Datta, Debayan; Symeonidi, Aikaterini; Castellanos, Andrés; Welz, Patrick-Simon; Caballero, Juan; Sassone–Corsi, Paolo; Muñoz‐Cánoves, Pura; Benitah, Salvador Aznar

doi:10.1016/j.cell.2017.07.035

Cited by 192 publications

(218 citation statements)

References 57 publications

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“…Another two recent studies show that epidermal as well as skeletal muscle stem cells retain robust circadian rhythms upon aging, but that the set of oscillatory output gene changes from genes involved in homeostasis to tissuespecific stress-associated genes involved in DNA damage and inefficient autophagy [73,74]. The authors could prevent age-associated rewiring of the circadian transcriptome by long-term caloric restriction in aged mice, which is line with an earlier found correlation between low-fat diet and reduced aging [73,75]. This means that stem cells can adapt their circadian transcriptome to different conditions of metabolic states and organ-specific stresses.…”

Section: Es Cells Differentiated Cellsmentioning

confidence: 99%

Circadian clocks: from stem cells to tissue homeostasis and regeneration

2017

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The circadian clock is an evolutionarily conserved timekeeper that adapts body physiology to diurnal cycles of around 24 h by influencing a wide variety of processes such as sleep‐to‐wake transitions, feeding and fasting patterns, body temperature, and hormone regulation. The molecular clock machinery comprises a pathway that is driven by rhythmic docking of the transcription factors BMAL1 and CLOCK on clock‐controlled output genes, which results in tissue‐specific oscillatory gene expression programs. Genetic as well as environmental perturbation of the circadian clock has been implicated in various diseases ranging from sleep to metabolic disorders and cancer development. Here, we review the origination of circadian rhythms in stem cells and their function in differentiated cells and organs. We describe how clocks influence stem cell maintenance and organ physiology, as well as how rhythmicity affects lineage commitment, tissue regeneration, and aging.

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Section: Es Cells Differentiated Cellsmentioning

confidence: 99%

Circadian clocks: from stem cells to tissue homeostasis and regeneration

2017

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“…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.…”

mentioning

confidence: 99%

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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“…Our study has identified that hippocampal NSCs exhibit early cellular aging ( Figure 3). To extend this phenotype, we compared NSC transcriptomes from the mature hippocampus (merged quiescent and active states) with published advanced age hematopoietic -hSC (Sun et al, 2014), muscle -mSC (Liu et al, 2013) and epidermal -eSC (Solanas et al, 2017) stem cell transcriptome datasets ( Figure 4A, Table S9). Fisher's exact tests were run on respective DEs to determine the degree of age-associated gene expression convergence between NSCs and other stem cell compartments.…”

Section: Consensus Signatures Of Stem Cell Agingmentioning

confidence: 99%

Early Stem Cell Aging in the Mature Brain

Ibrayeva

Bay

et al. 2019

Preprint

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Stem cell dysfunction drives many age-related disorders. Identifying mechanisms that initiate stem cell dysfunction represent early targets to enhance tissue resiliency throughout life. Here, we pinpoint multiple factors that compromise neural stem cell (NSC) behavior in the adult hippocampus. We find that NSCs exhibit asynchronous depletion by identifying short-term (ST-NSC) and intermediate-term NSCs (IT-NSCs). ST-NSC divide rapidly to generate neurons and deplete in the young brain. Meanwhile, multipotent IT-NSCs are maintained for months, but are pushed out of homeostasis by lengthening quiescence. Single cell transcriptome analysis of deep NSC quiescence revealed several hallmarks of cellular aging in the mature brain, including changes in tyrosine-protein kinases Abl1 and Abl2. Treatment with the Abl-inhibitor Imatinib was sufficient to overcome deep quiescence and restore NSC proliferation in the middle-aged brain. Further examination of mature NSC with old epidermal, hematopoietic and muscle stem cell transcriptomes identified consensus changes in stem cell aging. Our study elucidates multiple origins of adult neurogenesis decline and reveals that hippocampal NSCs are particularly vulnerable to a shared stem cell aging signature.

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Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress

Cited by 192 publications

References 57 publications

Circadian clocks: from stem cells to tissue homeostasis and regeneration

Circadian clocks: from stem cells to tissue homeostasis and regeneration

Calorie restriction reprograms diurnal rhythms in protein translation to regulate metabolism

Early Stem Cell Aging in the Mature Brain

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