Background: Exercise can mitigate the loss of muscle mass and function with ageing (Mikkelsen et al., 2017), although the protective effect of exercise specifically on muscle fibre denervation in humans has not received much attention. Similarly, muscle innervation status and satellite cells, which are interlinked (Borisov et al., 2001), have not been studied together in humans. Master athletes are commonly studied to decipher the relative contribution of ageing and inactivity to the age-related decline in muscle function (Lazarus & Harridge, 2017). However, this group is highly selected and represents a minor proportion of the general population. In contrast, more than 60% of people aged ≥60 are recreationally active (Hallal et al., 2012), underlining the relevance of studying this group. The purpose of this study was to investigate muscle function, denervation and satellite cell quantity and function in lifelong recreationally active elderly men, compared to sedentary young and elderly men.
Methods: Following ethical approval, 16 elderly men who had performed lifelong recreational exercise (73±4 y, LLEX), such as ball-games, resistance-exercise, racket-sports and cycling at non-competitive levels, were recruited. For comparison, 15 age matched sedentary individuals (73±4 y, SED), and 15 young sedentary individuals (26±5 y), were also recruited. Muscle function was evaluated by maximal voluntary contraction (MVC) and an acute bout of resistance exercise. Muscle biopsies were collected and analysed by immunofluorescence for markers of muscle fibre denervation (figure 1), satellite cell quantity and muscle fibre morphology. RT-qPCR was used to evaluate muscle innervation status, and primary cell cultures were established to test satellite cell function. Parametric (mean±SD) or nonparametric (median with range) statistical analyses were used, where data displayed a normal or skewed distribution, respectively.
Results: MVC was similar between LLEX and SED (204±41 vs. 186±50 Nm, p=0.291), but higher in young compared to old (318±75 vs. 196±46 Nm, p<0.001). Muscle function under challenged conditions was superior in LLEX compared to both SED and young (p<0.05). The proportion of denervated fibres was higher in old compared to young (1.03 [0-5.45] vs. 0.42 [0-1.40] % p=0.003), but was not different between LLEX and SED (0.996 [0-5.45] vs. 1.062 [0.33-4.08] %, P=0.984). In contrast, LLEX had higher mRNA levels of gamma (p=0.026) and beta (p=0.022) acetylcholine receptors (AChR) compared to SED, and the overall profile was remarkably similar between LLEX and young. LLEX had more type II fibre associated satellite cells compared to SED (0.061±0.021 vs. 0.045±0.012 %, p=0.016), whilst no differences in satellite cell function in vitro between the groups were observed. However, several age-related differences in satellite cell function were observed (myogenin, neonatal myosin, p16, p<0.05). Muscle fibre size was similar in LLEX and SED (3138±892 vs. 3107±1045 um2, p=0.930), but smaller in old compared to young (3123±953 vs. 5380±845 um2, p<0.001).
Conclusion: The muscle of lifelong recreationally active elderly men is characterized by a larger type II fibre associated satellite cell content, a youthful AChR profile, and better muscle function under challenged conditions. These findings indicate that recreational physical activity offers partial protection from muscle fibre denervation with ageing.