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DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress
The roles and regulatory mechanisms of transcriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age‐associated down‐regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF‐16, w...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516157/ https://www.ncbi.nlm.nih.gov/pubmed/30773782 http://dx.doi.org/10.1111/acel.12896 |
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author | Li, Shang‐Tong Zhao, Han‐Qing Zhang, Pan Liang, Chung‐Yi Zhang, Yan‐Ping Hsu, Ao‐Lin Dong, Meng‐Qiu |
author_facet | Li, Shang‐Tong Zhao, Han‐Qing Zhang, Pan Liang, Chung‐Yi Zhang, Yan‐Ping Hsu, Ao‐Lin Dong, Meng‐Qiu |
author_sort | Li, Shang‐Tong |
collection | PubMed |
description | The roles and regulatory mechanisms of transcriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age‐associated down‐regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF‐16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF‐16 translocates into the nucleus in aged wild‐type worms and activates the expression of hundreds of genes in response to age‐associated cellular stress. Most of the age‐dependent DAF‐16 targets are different from the canonical DAF‐16 targets downstream of insulin signaling. This and other evidence suggest that activation of DAF‐16 during aging is distinct from activation of DAF‐16 due to reduced signaling from DAF‐2. Further analysis showed that it is due in part to a loss of proteostasis during aging. We also found that without daf‐16, dramatic gene expression changes occur as early as on adult day 2, indicating that DAF‐16 acts to stabilize the transcriptome during normal aging. Our results thus reveal that normal aging is not simply a process in which the gene expression program descends into chaos due to loss of regulatory activities; rather, there is active transcriptional regulation during aging. |
format | Online Article Text |
id | pubmed-6516157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65161572019-06-01 DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress Li, Shang‐Tong Zhao, Han‐Qing Zhang, Pan Liang, Chung‐Yi Zhang, Yan‐Ping Hsu, Ao‐Lin Dong, Meng‐Qiu Aging Cell Original Papers The roles and regulatory mechanisms of transcriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age‐associated down‐regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF‐16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF‐16 translocates into the nucleus in aged wild‐type worms and activates the expression of hundreds of genes in response to age‐associated cellular stress. Most of the age‐dependent DAF‐16 targets are different from the canonical DAF‐16 targets downstream of insulin signaling. This and other evidence suggest that activation of DAF‐16 during aging is distinct from activation of DAF‐16 due to reduced signaling from DAF‐2. Further analysis showed that it is due in part to a loss of proteostasis during aging. We also found that without daf‐16, dramatic gene expression changes occur as early as on adult day 2, indicating that DAF‐16 acts to stabilize the transcriptome during normal aging. Our results thus reveal that normal aging is not simply a process in which the gene expression program descends into chaos due to loss of regulatory activities; rather, there is active transcriptional regulation during aging. John Wiley and Sons Inc. 2019-02-17 2019-06 /pmc/articles/PMC6516157/ /pubmed/30773782 http://dx.doi.org/10.1111/acel.12896 Text en © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Papers Li, Shang‐Tong Zhao, Han‐Qing Zhang, Pan Liang, Chung‐Yi Zhang, Yan‐Ping Hsu, Ao‐Lin Dong, Meng‐Qiu DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress |
title | DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress |
title_full | DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress |
title_fullStr | DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress |
title_full_unstemmed | DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress |
title_short | DAF‐16 stabilizes the aging transcriptome and is activated in mid‐aged Caenorhabditis elegans to cope with internal stress |
title_sort | daf‐16 stabilizes the aging transcriptome and is activated in mid‐aged caenorhabditis elegans to cope with internal stress |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516157/ https://www.ncbi.nlm.nih.gov/pubmed/30773782 http://dx.doi.org/10.1111/acel.12896 |
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