Therapeutic potential of nicotinamide and ABT263 in alcohol-associated liver disease through targeting cellular senescence.

ABSTRACT: Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, yet clinically effective therapies for ALD remain lacking. Here, we demonstrate that alcohol intake and its metabolite, acetaldehyde (ACH), induce senescence in the liver and liver cells, respectively. To assess the therapeutic potential of targeting liver senescence in ALD, we treated ALD-affected mice with the senolytic compound ABT263 and the senomorphic NAD⁺ precursor, nicotinamide (NAM). The results show that ABT263 effectively clears senescent hepatocytes and stellate cells, and reduces liver triglyceride (TG), but increases plasma alanine aminotransferase and TG levels. Conversely, NAM efficiently suppresses senescence and the senescence-associated secretory phenotype (SASP),

SUBMITTER: Gold NM 

PROVIDER: S-EPMC11808045 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature