Accelerated aging of skeletal muscle and the immune system in patients with chronic liver disease

Abstract

Patients with chronic liver disease (CLD) often present with significant frailty, sarcopenia, and impaired immune function. However, the mechanisms driving the development of these age-related phenotypes are not fully understood. To determine whether accelerated biological aging may play a role in CLD, epigenetic, transcriptomic, and phenotypic assessments were performed on the skeletal muscle tissue and immune cells of CLD patients and age-matched healthy controls. Accelerated biological aging of the skeletal muscle tissue of CLD patients was detected, as evidenced by an increase in epigenetic age compared with chronological age (mean +2.2 ± 4.8 years compared with healthy controls at −3.0 ± 3.2 years, p = 0.0001). Considering disease etiology, age acceleration was significantly greater in both the alcohol-related (ArLD) (p = 0.01) and nonalcoholic fatty liver disease (NAFLD) (p = 0.0026) subgroups than in the healthy control subgroup, with no age acceleration observed in the immune-mediated subgroup or healthy control subgroup (p = 0.3). The skeletal muscle transcriptome was also enriched for genes associated with cellular senescence. Similarly, blood cell epigenetic age was significantly greater than that in control individuals, as calculated using the PhenoAge (p < 0.0001), DunedinPACE (p < 0.0001), or Hannum (p = 0.01) epigenetic clocks, with no difference using the Horvath clock. Analysis of the IMM-Age score indicated a prematurely aged immune phenotype in CLD patients that was 2-fold greater than that observed in age-matched healthy controls (p < 0.0001). These findings suggested that accelerated cellular aging may contribute to a phenotype associated with advanced age in CLD patients. Therefore, therapeutic interventions to reduce biological aging in CLD patients may improve health outcomes. Chronic liver disease, a long-term condition damaging the liver, is causing more deaths worldwide. Patients often develop immune dysfunction and sarcopenia. This study aimed to see if CLD patients show signs of fast biological ageing, particularly in muscles and the immune system. The research compared CLD patients to healthy people, looking at muscle samples, blood samples, and immune cells to check for ageing signs. Results showed that CLD patients have faster biological ageing in muscles and immune cells, with increased epigenetic age and more senescence-associated genes. This suggests that CLD speeds up the ageing process, which could explain the common occurrence of sarcopenia and immune dysfunction in these patients. Future implications include the possibility of developing treatments targeting the ageing process in CLD patients, offering hope for better health and quality of life This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.