| First Author | Zhu P | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 2568 |
| PubMed ID | 31189923 | Mgi Jnum | J:283540 |
| Mgi Id | MGI:6323909 | Doi | 10.1038/s41467-019-10479-4 |
| Citation | Zhu P, et al. (2019) The transcription factor Slug represses p16(Ink4a) and regulates murine muscle stem cell aging. Nat Commun 10(1):2568 |
| abstractText | Activation of the p16(Ink4a)-associated senescence pathway during aging breaks muscle homeostasis and causes degenerative muscle disease by irreversibly dampening satellite cell (SC) self-renewal capacity. Here, we report that the zinc-finger transcription factor Slug is highly expressed in quiescent SCs of mice and functions as a direct transcriptional repressor of p16(Ink4a). Loss of Slug promotes derepression of p16(Ink4a) in SCs and accelerates the entry of SCs into a fully senescent state upon damage-induced stress. p16(Ink4a) depletion partially rescues defects in Slug-deficient SCs. Furthermore, reduced Slug expression is accompanied by p16(Ink4a) accumulation in aged SCs. Slug overexpression ameliorates aged muscle regeneration by enhancing SC self-renewal through active repression of p16(Ink4a) transcription. Our results identify a cell-autonomous mechanism underlying functional defects of SCs at advanced age. As p16(Ink4a) dysregulation is the chief cause for regenerative defects of human geriatric SCs, these findings highlight Slug as a potential therapeutic target for aging-associated degenerative muscle disease. |
