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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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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. |
format | Online Article Text |
id | pubmed-10557775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
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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