論文 - 詳細
| RRC ID | 82110 |
|---|---|
| 著者 | Odawara T, Yamauchi S, Ichijo H. |
| タイトル | Apoptosis signal-regulating kinase 1 promotes inflammation in senescence and aging. |
| ジャーナル | Commun Biol |
| Abstract |
Cellular senescence is a stress-induced, permanent cell cycle arrest involved in tumor suppression and aging. Senescent cells secrete bioactive molecules such as pro-inflammatory cytokines and chemokines. This senescence-associated secretory phenotype (SASP) has been implicated in immune-mediated elimination of senescent cells and age-associated chronic inflammation. However, the mechanisms regulating the SASP are incompletely understood. Here, we show that the stress-responsive kinase apoptosis signal-regulating kinase 1 (ASK1) promotes inflammation in senescence and aging. ASK1 is activated during senescence and increases the expression of pro-inflammatory cytokines and chemokines by activating p38, a kinase critical for the SASP. ASK1-deficient mice show impaired elimination of oncogene-induced senescent cells and an increased rate of tumorigenesis. Furthermore, ASK1 deficiency prevents age-associated p38 activation and inflammation and attenuates glomerulosclerosis. Our results suggest that ASK1 is a driver of the SASP and age-associated chronic inflammation and represents a potential therapeutic target for age-related diseases. |
| 巻・号 | 7(1) |
| ページ | 691 |
| 公開日 | 2024-6-5 |
| DOI | 10.1038/s42003-024-06386-0 |
| PII | 10.1038/s42003-024-06386-0 |
| PMID | 38839869 |
| PMC | PMC11153534 |
| MeSH | Aging* Animals Cellular Senescence* Cytokines / genetics Cytokines / metabolism Humans Inflammation* / metabolism MAP Kinase Kinase Kinase 5* / genetics MAP Kinase Kinase Kinase 5* / metabolism Mice Mice, Inbred C57BL Mice, Knockout Senescence-Associated Secretory Phenotype / genetics p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 4.165 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |