Accelerated ageing 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 ageing may play a role, we performed an epigenetic, transcriptomic and phenotypic assessment of the biological age of skeletal muscle tissue and immune cells of CLD patients. We identified accelerated biological ageing of the skeletal muscle tissue of CLD patients, evidenced by accelerated epigenetic ageing and a transcriptome enriched for cellular senescence. This was accompanied by a prematurely aged immune phenotype, with CLD patients presenting with an accelerated ageing trajectory within the adaptive arm of the immune system. Inherent accelerated cellular ageing may contribute to the early onset of age-associated diseases in CLD patients and therefore therapeutic intervention to reduce biological ageing in CLD may improve to health outcomes.