Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPα-p300 Axis.

ABSTRACT: 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/EBPα-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/EBPα-S193A mice do not develop hepatic steatosis with advancing age. Underlying mechanisms include a block in C/EBPα 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/EBPα-p300 complexes and eliminates hepatic steatosis. Moreover, the inhibition of cdk4 in aged mice reverses man

SUBMITTER: Nguyen P 

PROVIDER: S-EPMC8209958 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature