Role of accelerated ageing in limb muscle wasting of patients with Chronic Obstructive Pulmonary Disease (COPD)

Abstract

Skeletal muscle wasting is an independent predictor of health-related quality of life, and survival in COPD, but the complexity of the molecular mechanisms associated with this process have not been fully elucidated. We aimed to determine whether an impaired ability to repair DNA damage contributes to muscle wasting and the accelerated ageing phenotype in patients with COPD. These data support the publication: Role of accelerated ageing in limb muscle wasting of patients with Chronic Obstructive Pulmonary Disease (COPD). Ramzi Lakhdar, Dagmara McGuinness, Ellen M Drost, Paul G Shiels,Ricardo Bastos, William MacNee and Roberto A Rabinovich. International Journal of COPD 2018 (Accepted manuscript).

We observed a decrease in γH2AX expression in COPDL, which occurred in association with a tendency to increase in CDKN2A/p16ink4a and a significant decrease in SIRT1 and SIRT6 protein levels. Cellular damage and muscle inflammatory markers were also increased in COPDL.

These data are in keeping with an accelerated ageing phenotype as a result of impaired DNA repair and dysregulation of cellular homeostasis in the muscle of COPD patients with a low FFMI. These data indicate cellular degeneration via stress-induced premature senescence and associated inflammatory responses abetted by the senescence-associated secretory phenotype and reflected an increased expression of markers of oxidative stress and inflammation.