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Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms

Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent changes in peripheral rhythms, we compared the ability of human serum from...

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Autores principales: Schwarz, Jessica E., Mrčela, Antonijo, Lahens, Nicholas F., Li, Yongjun, Hsu, Cynthia T., Grant, Gregory, Skarke, Carsten, Zhang, Shirley L., Sehgal, Amita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557775/
https://www.ncbi.nlm.nih.gov/pubmed/37808824
http://dx.doi.org/10.1101/2023.04.19.537477
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author Schwarz, Jessica E.
Mrčela, Antonijo
Lahens, Nicholas F.
Li, Yongjun
Hsu, Cynthia T.
Grant, Gregory
Skarke, Carsten
Zhang, Shirley L.
Sehgal, Amita
author_facet Schwarz, Jessica E.
Mrčela, Antonijo
Lahens, Nicholas F.
Li, Yongjun
Hsu, Cynthia T.
Grant, Gregory
Skarke, Carsten
Zhang, Shirley L.
Sehgal, Amita
author_sort Schwarz, Jessica E.
collection PubMed
description Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent changes in peripheral rhythms, we compared the ability of human serum from young and old individuals to synchronize circadian rhythms in culture. We collected blood from apparently healthy young (age 25–30) and old (age 70–76) individuals and used the serum to synchronize cultured fibroblasts. We found that young and old sera are equally competent at driving robust ~24h oscillations of a luciferase reporter driven by clock gene promoter. However, cyclic gene expression is affected, such that young and old sera drive cycling of different genes. While genes involved in the cell cycle and transcription/translation remain rhythmic in both conditions, genes identified by STRING and IPA analyses as associated with oxidative phosphorylation and Alzheimer’s Disease lose rhythmicity in the aged condition. Also, the expression of cycling genes associated with cholesterol biosynthesis increases in the cells entrained with old serum. We did not observe a global difference in the distribution of phase between groups, but find that peak expression of several clock controlled genes (PER3, NR1D1, NR1D2, CRY1, CRY2, and TEF) lags in the cells synchronized with old serum. Taken together, these findings demonstrate that age-dependent blood-borne factors affect peripheral circadian rhythms in cells and have the potential to impact health and disease via maintaining or disrupting rhythms respectively.
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spelling pubmed-105577752023-10-07 Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms Schwarz, Jessica E. Mrčela, Antonijo Lahens, Nicholas F. Li, Yongjun Hsu, Cynthia T. Grant, Gregory Skarke, Carsten Zhang, Shirley L. Sehgal, Amita bioRxiv Article Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent changes in peripheral rhythms, we compared the ability of human serum from young and old individuals to synchronize circadian rhythms in culture. We collected blood from apparently healthy young (age 25–30) and old (age 70–76) individuals and used the serum to synchronize cultured fibroblasts. We found that young and old sera are equally competent at driving robust ~24h oscillations of a luciferase reporter driven by clock gene promoter. However, cyclic gene expression is affected, such that young and old sera drive cycling of different genes. While genes involved in the cell cycle and transcription/translation remain rhythmic in both conditions, genes identified by STRING and IPA analyses as associated with oxidative phosphorylation and Alzheimer’s Disease lose rhythmicity in the aged condition. Also, the expression of cycling genes associated with cholesterol biosynthesis increases in the cells entrained with old serum. We did not observe a global difference in the distribution of phase between groups, but find that peak expression of several clock controlled genes (PER3, NR1D1, NR1D2, CRY1, CRY2, and TEF) lags in the cells synchronized with old serum. Taken together, these findings demonstrate that age-dependent blood-borne factors affect peripheral circadian rhythms in cells and have the potential to impact health and disease via maintaining or disrupting rhythms respectively. Cold Spring Harbor Laboratory 2023-04-20 /pmc/articles/PMC10557775/ /pubmed/37808824 http://dx.doi.org/10.1101/2023.04.19.537477 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Schwarz, Jessica E.
Mrčela, Antonijo
Lahens, Nicholas F.
Li, Yongjun
Hsu, Cynthia T.
Grant, Gregory
Skarke, Carsten
Zhang, Shirley L.
Sehgal, Amita
Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
title Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
title_full Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
title_fullStr Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
title_full_unstemmed Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
title_short Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
title_sort evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557775/
https://www.ncbi.nlm.nih.gov/pubmed/37808824
http://dx.doi.org/10.1101/2023.04.19.537477
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