CDK4 and metabolic dysfunction-associated steatotic liver disease: Senescence markers (p16, p21, and p53) have been identified in hepatocytes of NAFLD, and hepatocyte senescence correlates with the progression of NAFLD.312,313 Deletion of p16Ink4a-expressing senescent hepatocytes in INK-ATTAC mice significantly reduces hepatic lipid accumulation.314,315 Cyclin-dependent kinase-4 (CDK4) may be inhibited by p16 to maintain the senescent phenotype.