Glycyl-l-histidyl-l-lysine-Cu(2+) rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway

Deng M, Zhang Q, Yan L, Bian Y, Li R, Gao J, Wang Y, Miao J, Li J, Zhou X, Hou G · Journal of Cachexia, Sarcopenia and Muscle

Plasma GHK was lower in COPD than in age-matched controls (70.27 ± 38.87 against 133.0 ± 54.54 ng/mL, P=0.009), and within the nine patients it tracked pectoralis muscle area (R=0.684, P=0.042), TNF-α (R=−0.696, P=0.037) and SOD2 (R=0.721, P=0.029). In smoke-exposed mice, GHK-Cu at 0.2 and 2 mg/kg preserved skeletal muscle weight (1.19% untreated against 1.29% and 1.40%), fibre cross-sectional area (1055 against 1797 and 2252 µm²) and grip strength (175.5 against 257.6 and 339.1 g), each dose-dependently. SIRT1 expression and deacetylase activity were measured and rose with dose, and a SIRT1 inhibitor abolished the protection; the binding itself is a docking prediction at −6.1 kcal/mol rather than a measurement.

Population

9 patients with COPD and 11 age-matched healthy controls for plasma measurement; C2C12 myotubes and cigarette-smoke-exposed C57BL/6 mice for the intervention

Intervention

GHK-Cu 0.2 and 2 mg/kg in smoke-exposed mice; GHK-Cu on smoke-extract-treated myotubes

Comparator

Untreated smoke-exposed animals and cells

Limitations

The human component is a 20-person cross-sectional plasma measurement rather than a trial, its contrast is disease rather than age, and the three correlations rest on the nine patients with COPD. The intervention data are entirely rodent and cell culture, in a smoking model of muscle wasting with no joint or cartilage endpoint. Publicly funded, with no conflict of interest declared.