Neither Myonuclear Accretion nor a Myonuclear Domain Size Ceiling is a Feature of the Attenuated Hypertrophic Potential of Aged Human Skeletal Muscle

Ageing limits growth capacity of skeletal muscle (e.g. in response to resistance exercise), but the role of satellite cell (SC) function in driving this phenomenon is poorly defined. Younger (Y) (~ 23 years) and older (O) men (~ 69 years) (normal-weight BMI) underwent 6 weeks of unilateral resistance exercise training (RET). Muscle biopsies were taken at baseline and after 3-/6-week training. We determined muscle size by fibre CSA (and type), SC number, myonuclei counts and DNA synthesis (via DO ingestion). At baseline, there were no significant differences in fibre areas between Y and O. RET increased type I fibre area in Y from baseline at both 3 weeks and 6 weeks (baseline: 4509 ± 534 µm, 3 weeks; 5497 ± 510 µm P < 0.05, 6 weeks; 5402 ± 352 µm P < 0.05), whilst O increased from baseline at 6 weeks only (baseline 5120 ± 403 µm, 3 weeks; 5606 ± 620 µm, 6 weeks; 6017 ± 482 µm P < 0.05). However, type II fibre area increased from baseline in Y at both 3 weeks and 6 weeks (baseline: 4949 ± 459 µm, 3 weeks; 6145 ± 484 µm (P < 0.01), 6 weeks; 5992 ± 491 µm (P < 0.01), whilst O showed no change (baseline 5210 ± 410 µm, 3 weeks; 5356 ± 535 µm (P = 0.9), 6 weeks; 5857 ± 478 µm (P = 0.1). At baseline, there were no differences in fibre myonuclei number between Y and O. RET increased type I fibre myonuclei number from baseline in both Y and O at 3 weeks and 6 weeks with RET (younger: baseline 2.47 ± 0.16, 3 weeks; 3.19 ± 0.16 (P < 0.001), 6 weeks; 3.70 ± 0.29 (P < 0.0001); older: baseline 2.29 ± 0.09, 3 weeks; 3.01 ± 0.09 (P < 0.001), 6 weeks; 3.65 ± 0.18 (P < 0.0001)). Similarly, type II fibre myonuclei number increased from baseline in both Y and O at 3 weeks and 6 weeks (younger: baseline 2.49 ± 0.14, 3 weeks; 3.31 ± 0.21 (P < 0.001), 6 weeks; 3.86 ± 0.29 (P < 0.0001); older: baseline 2.43 ± 0.12, 3 weeks; 3.37 ± 0.12 (P < 0.001), 6 weeks; 3.81 ± 0.15 (P < 0.0001)). DNA synthesis rates %.d exhibited a main effect of training but no age discrimination. Declines in myonuclei addition do not underlie impaired muscle growth capacity in older humans, supporting ribosomal and proteostasis impairments as we have previously reported.