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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Federation of American Society of Experimental Biology
2019
|
| _version_ | 1826282340716904448 |
|---|---|
| author | Baker, JR Vuppusetty, C Colley, T Hassibi, S Fenwick, PS Donnelly, LE Ito, K Barnes, PJ |
| author_facet | Baker, JR Vuppusetty, C Colley, T Hassibi, S Fenwick, PS Donnelly, LE Ito, K Barnes, PJ |
| author_sort | Baker, JR |
| collection | OXFORD |
| 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 (p16INK4a, p21Waf1, and p27Kip1), 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. |
| first_indexed | 2024-03-07T00:42:22Z |
| format | Journal article |
| id | oxford-uuid:838234c6-49f1-4062-ab73-f764a7f3fe10 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:42:22Z |
| publishDate | 2019 |
| publisher | Federation of American Society of Experimental Biology |
| record_format | dspace |
| spelling | oxford-uuid:838234c6-49f1-4062-ab73-f764a7f3fe102022-03-26T21:44:32ZMicroRNA-570 is a novel regulator of cellular senescence and inflammagingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:838234c6-49f1-4062-ab73-f764a7f3fe10EnglishSymplectic Elements at OxfordFederation of American Society of Experimental Biology2019Baker, JRVuppusetty, CColley, THassibi, SFenwick, PSDonnelly, LEIto, KBarnes, PJDiseases 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 (p16INK4a, p21Waf1, and p27Kip1), 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. |
| spellingShingle | Baker, JR Vuppusetty, C Colley, T Hassibi, S Fenwick, PS Donnelly, LE Ito, K Barnes, PJ 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 |
| work_keys_str_mv | AT bakerjr microrna570isanovelregulatorofcellularsenescenceandinflammaging AT vuppusettyc microrna570isanovelregulatorofcellularsenescenceandinflammaging AT colleyt microrna570isanovelregulatorofcellularsenescenceandinflammaging AT hassibis microrna570isanovelregulatorofcellularsenescenceandinflammaging AT fenwickps microrna570isanovelregulatorofcellularsenescenceandinflammaging AT donnellyle microrna570isanovelregulatorofcellularsenescenceandinflammaging AT itok microrna570isanovelregulatorofcellularsenescenceandinflammaging AT barnespj microrna570isanovelregulatorofcellularsenescenceandinflammaging |