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MicroRNA-570 is a novel regulator of cellular senescence and inflammaging
Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs. Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases. Diseases of accelerate...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338629/ https://www.ncbi.nlm.nih.gov/pubmed/30156909 http://dx.doi.org/10.1096/fj.201800965R |
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author | Baker, Jonathan R. Vuppusetty, Chaitanya Colley, Thomas Hassibi, Shyreen Fenwick, Peter S. Donnelly, Louise E. Ito, Kazuhiro Barnes, Peter J. |
author_facet | Baker, Jonathan R. Vuppusetty, Chaitanya Colley, Thomas Hassibi, Shyreen Fenwick, Peter S. Donnelly, Louise E. Ito, Kazuhiro Barnes, Peter J. |
author_sort | Baker, Jonathan R. |
collection | PubMed |
description | Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs. Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases. Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells. These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease. Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1. MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1. Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16(INK4a), p21(Waf1), and p27(Kip1)), thereby restoring cellular growth by allowing progression through the cell cycle. MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6). Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.—Baker, J. R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P. S., Donnelly, L. E., Ito, K., Barnes, P. J. MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. |
format | Online Article Text |
id | pubmed-6338629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-63386292019-01-24 MicroRNA-570 is a novel regulator of cellular senescence and inflammaging Baker, Jonathan R. Vuppusetty, Chaitanya Colley, Thomas Hassibi, Shyreen Fenwick, Peter S. Donnelly, Louise E. Ito, Kazuhiro Barnes, Peter J. FASEB J Research Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs. Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases. Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells. These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease. Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1. MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1. Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16(INK4a), p21(Waf1), and p27(Kip1)), thereby restoring cellular growth by allowing progression through the cell cycle. MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6). Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.—Baker, J. R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P. S., Donnelly, L. E., Ito, K., Barnes, P. J. MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. Federation of American Societies for Experimental Biology 2019-02 2018-08-29 /pmc/articles/PMC6338629/ /pubmed/30156909 http://dx.doi.org/10.1096/fj.201800965R Text en © The Author(s) https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Baker, Jonathan R. Vuppusetty, Chaitanya Colley, Thomas Hassibi, Shyreen Fenwick, Peter S. Donnelly, Louise E. Ito, Kazuhiro Barnes, Peter J. MicroRNA-570 is a novel regulator of cellular senescence and inflammaging |
title | MicroRNA-570 is a novel regulator of cellular senescence and inflammaging |
title_full | MicroRNA-570 is a novel regulator of cellular senescence and inflammaging |
title_fullStr | MicroRNA-570 is a novel regulator of cellular senescence and inflammaging |
title_full_unstemmed | MicroRNA-570 is a novel regulator of cellular senescence and inflammaging |
title_short | MicroRNA-570 is a novel regulator of cellular senescence and inflammaging |
title_sort | microrna-570 is a novel regulator of cellular senescence and inflammaging |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338629/ https://www.ncbi.nlm.nih.gov/pubmed/30156909 http://dx.doi.org/10.1096/fj.201800965R |
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