Ageing liver in the era of MASLD: risks, mechanisms and treatment opportunities

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-quarter of the adult population. While most research has focused on middle-aged individuals, MASLD in elderly adults is increasingly recognised, but data on concrete risks, mechanisms and treatment options remain scarce. With an emphasis on age-specific diagnostic difficulties, multimorbidity and treatment considerations, this review summarises the most recent data on the epidemiology, pathophysiology and clinical management of MASLD in people aged 65 and older. The progression of MASLD is driven by age-related mechanisms, including telomere shortening, mitochondrial dysfunction, reduced autophagy and epigenetic drift. At the same time, frailty, polypharmacy and alterations in body composition, particularly the increased fat-to-lean mass ratio, complicate the diagnosis and treatment of MASLD. The need for age-adjusted thresholds is highlighted by the tendency of non-invasive fibrosis scoring systems, such as fibrosis-4 index, to overestimate fibrosis in elderly patients. Younger patients experience the greatest loss of life years due to MASLD, but elderly individuals are more susceptible to severe outcomes due to sarcopenia and multimorbidity. The primary therapy for MASLD remains lifestyle modification, but it requires careful fine-tuning to prevent malnutrition in elderly adults. Novel therapies such as resmetirom and glucagon-like peptide-1 receptor agonists show promising efficacy, but clinical trials often exclude elderly participants. Improving outcomes will require effective prevention strategies, age-adapted diagnostic algorithms and inclusion of the elderly population in clinical research. This review provides a framework for age-sensitive MASLD care while highlighting priorities for future translational studies.