Satellite Cells Senescence in Limb Muscle of Severe Patients with COPD

RATIONALE: The maintenance of peripheral muscle mass may be compromised in chronic obstructive pulmonary disease (COPD) due to premature cellular senescence and exhaustion of the regenerative potential of the muscles. METHODS: Vastus lateralis biopsies were obtained from patients with COPD (n = 16) and healthy subjects (n = 7). Satellite cell number and the proportion of central nuclei, as a marker of muscle regenerative events, were assessed on cryosections. Telomere lengths, used as a marker of cellular senescence, were determined using Southern blot analyses. RESULTS: Central nuclei proportion was significantly higher in patients with COPD with a preserved muscle mass compared to controls and patients with COPD with muscle atrophy (p<0.001). In COPD, maximal telomere length was significantly decreased compared to controls (p<0.05). Similarly, minimal telomere length was significantly reduced in GOLD III–IV patients with muscle atrophy compared to controls (p<0.005). Minimal, mean and maximum telomere lengths correlated with mid-thigh muscle cross-sectional area (MTCSA) (R = 0.523, p = 0.005; R = 0.435, p = 0.019 and R = 0.491, p = 0.009, respectively). CONCLUSIONS: Evidence of increased regenerative events was seen in GOLD III–IV patients with preserved muscle mass. Shortening of telomeres in GOLD III–IV patients with muscle atrophy is consistent with an increased number of senescent satellite cells and an exhausted muscle regenerative capacity, compromising the maintenance of muscle mass in these individuals.