論文 - 詳細
| RRC ID | 63340 |
|---|---|
| 著者 | Johmura Y, Yamanaka T, Omori S, Wang TW, Sugiura Y, Matsumoto M, Suzuki N, Kumamoto S, Yamaguchi K, Hatakeyama S, Takami T, Yamaguchi R, Shimizu E, Ikeda K, Okahashi N, Mikawa R, Suematsu M, Arita M, Sugimoto M, Nakayama KI, Furukawa Y, Imoto S, Nakanishi M. |
| タイトル | Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. |
| ジャーナル | Science |
| Abstract |
Removal of senescent cells (senolysis) has been proposed to be beneficial for improving age-associated pathologies, but the molecular pathways for such senolytic activity have not yet emerged. Here, we identified glutaminase 1 (GLS1) as an essential gene for the survival of human senescent cells. The intracellular pH in senescent cells was lowered by lysosomal membrane damage, and this lowered pH induced kidney-type glutaminase (KGA) expression. The resulting enhanced glutaminolysis induced ammonia production, which neutralized the lower pH and improved survival of the senescent cells. Inhibition of KGA-dependent glutaminolysis in aged mice eliminated senescent cells specifically and ameliorated age-associated organ dysfunction. Our results suggest that senescent cells rely on glutaminolysis, and its inhibition offers a promising strategy for inducing senolysis in vivo. |
| 巻・号 | 371(6526) |
| ページ | 265-270 |
| 公開日 | 2021-1-15 |
| DOI | 10.1126/science.abb5916 |
| PII | 371/6526/265 |
| PMID | 33446552 |
| MeSH | Adipose Tissue / enzymology Aging / genetics Aging / metabolism* Ammonia / metabolism Animals Cell Survival Cellular Senescence / genetics Cellular Senescence / physiology* Genes, Essential Glutaminase / genetics Glutaminase / metabolism* Humans Hydrogen-Ion Concentration Lung / enzymology Male Mice Mice, Inbred C57BL Skin / enzymology |
| IF | 41.846 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 406 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 13.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |