Analysis of 19 studies reveals that accelerated biological aging—measured through epigenetic clocks, telomere length, and clinical composite indices like PhenoAge and Klemera-Doubal method—consistently predicts higher odds of metabolic dysfunction-associated steatotic liver disease (MASLD), greater fibrosis severity, and increased all-cause mortality. Mendelian randomization analyses suggest cellular aging may causally contribute to liver fibrogenesis rather than merely reflecting disease consequences.
This evidence positions biological aging as a fundamental upstream driver of liver pathology, challenging the traditional view that fatty liver disease primarily stems from metabolic factors alone. The finding that aging biomarkers predict incident NAFLD in prospective cohorts suggests these measures could identify at-risk individuals before overt disease develops. This represents a paradigm shift toward viewing liver disease through a geroscience lens, where targeting aging mechanisms—rather than just metabolic dysfunction—could prevent or reverse hepatic deterioration. The mediating role of biological age in environmental toxicant effects on liver health adds another layer of clinical relevance, particularly for populations with high exposure burdens.
