Journal article
Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging
Cell, Vol.170(4), pp.664-677.e11
08/10/2017
DOI: 10.1016/j.cell.2017.07.042
PMID: 28802039
Abstract
The process of aging and circadian rhythms are intimately intertwined, but how peripheral clocks involved in metabolic homeostasis contribute to aging remains unknown. Importantly, caloric restriction (CR) extends lifespan in several organisms and rewires circadian metabolism. Using young versus old mice, fed ad libitum or under CR, we reveal reprogramming of the circadian transcriptome in the liver. These age-dependent changes occur in a highly tissue-specific manner, as demonstrated by comparing circadian gene expression in the liver versus epidermal and skeletal muscle stem cells. Moreover, de novo oscillating genes under CR show an enrichment in SIRT1 targets in the liver. This is accompanied by distinct circadian hepatic signatures in NAD+-related metabolites and cyclic global protein acetylation. Strikingly, this oscillation in acetylation is absent in old mice while CR robustly rescues global protein acetylation. Our findings indicate that the clock operates at the crossroad between protein acetylation, liver metabolism, and aging. [Display omitted] •Aging reprograms clockwork with distinct modalities in the liver versus stem cells•Liver circadian genomic signatures of aging are reverted by caloric restriction (CR)•Cyclic protein acetylation is lost in old mice while CR results in hyperacetylation•CR reorganizes circadian metabolic pathway linked to NAD+-SIRT1-AceCS1 in the liver Aging reprograms the circadian transcriptome in a highly tissue-specific manner
Details
- Title: Subtitle
- Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging
- Creators
- Shogo Sato - Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine, Irvine, CA 92607, USAGuiomar Solanas - Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, 08028, Barcelona, SpainFrancisca Oliveira Peixoto - Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, 08028, Barcelona, SpainLeonardo Bee - Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine, Irvine, CA 92607, USAAikaterini Symeonidi - Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, 08028, Barcelona, SpainMark S Schmidt - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USACharles Brenner - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USASelma Masri - Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine, Irvine, CA 92607, USASalvador Aznar Benitah - Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, 08028, Barcelona, SpainPaolo Sassone-Corsi - Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine, Irvine, CA 92607, USA
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.170(4), pp.664-677.e11
- DOI
- 10.1016/j.cell.2017.07.042
- PMID
- 28802039
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Grant note
- name: Della Martin Foundation; DOI: 10.13039/501100005010, name: Italian Association for Cancer Research; DOI: 10.13039/100000002, name: National Institutes of Health; name: INSERM (Institut National de la Sante et Recherche Medicale; name: Roy J. Carver Trust; name: Novo Nordisk Foundation Challenge Grant; DOI: 10.13039/501100000781, name: European Research Council (ERC); name: Spanish Ministry of Economy and Development; name: Institute for Research in Biomedicine (IRB-Barcelona); name: La Caixa International PhD fellowship; name: MINECO
- Language
- English
- Date published
- 08/10/2017
- Academic Unit
- Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9983788596202771
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