| First Author | Nguyen P | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 6 | Pages | 1597-1609 |
| PubMed ID | 30089269 | Mgi Jnum | J:271103 |
| Mgi Id | MGI:6278428 | Doi | 10.1016/j.celrep.2018.07.014 |
| Citation | Nguyen P, et al. (2018) Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPalpha-p300 Axis. Cell Rep 24(6):1597-1609 |
| abstractText | The aging liver is affected by several disorders, including steatosis, that can lead to a decline of liver functions. Here, we present evidence that the cdk4-C/EBPalpha-p300 axis is a critical regulator of age-associated disorders, including steatosis. We found that patients with non-alcoholic fatty liver disease (NAFLD) have increased levels of cdk4 and that cdk4-resistant C/EBPalpha-S193A mice do not develop hepatic steatosis with advancing age. Underlying mechanisms include a block in C/EBPalpha activation and subsequent failure in activation of enzymes involved in the development of NAFLD. Inhibition of cdk4 in aged wild-type (WT) mice by a specific cdk4 inhibitor, PD-0332991, reduces C/EBPalpha-p300 complexes and eliminates hepatic steatosis. Moreover, the inhibition of cdk4 in aged mice reverses many age-related disorders. Mechanisms of correction include elimination of cellular senescence and alterations in the chromatin structure of hepatocytes. Thus, the inhibition of cdk4 might be considered as a therapeutic approach to correct age-associated liver disorders. |
