Ageing is associated with a general reduction of physiological function and a reduction of muscle mass and strength. Endocrine factors such as myostatin, activin A, growth and differentiation factor 11 (GDF-11) and their inhibitory peptides influence muscle mass in health and disease. We hypothesised that myocytes cultured in plasma from older and younger individuals would show an ageing effect, with reduced proliferation and differentiation in older environments. C2C12 myoblasts were grown as standard and stimulated with media conditioned with 5% plasma from healthy male participants that were either younger (n = 6, 18–35 years of age) or older (n = 6, >57 years of age). Concentration of plasma myostatin (total and free), follistatin-like binding protein (FLRG), GDF-11 and activin A were quantified by ELISA. Both FLRG and activin A were elevated in older individuals (109.6 and 35.1% increase, respectively), whilst myostatin (free and total) and GDF-11 were not. Results indicated that plasma activin A and FLRG were increased in older vs. younger participants, GDF11 and myostatin did not differ. Myoblasts in vitro showed no difference in proliferation rate between ages, however scratch closure was greater in younger vs. older plasma stimulated myoblasts (78.2 vs. 87.2% of baseline scratch diameter, respectively). Myotube diameters were larger in cells stimulated with younger plasma than with older at 24 and 48 h, but not at 2 h. A significant negative correlation was noted between in vivo plasma FLRG concentration and in vitro myotube diameter 48 h following plasma stimulation (r2 = 0.392, p = 0.030). Here we show that myoblasts and myotubes cultured in media conditioned with plasma from younger or older individuals show an ageing effect, and further this effect moderately correlates with circulating FLRG concentration in vivo. The effect of ageing on muscle function may not be innate to the tissue, but involve a general cellular environment change. Further work is needed to examine the effect of increased FLRG concentration on muscle function in ageing populations.

Loss of muscle mass and function are a well‐defined aspect of human aging from the 3rd decade of life, which result in reduced independence and increased mortality. The activin family of peptides contains several endocrine factors (activin A, myostatin, growth and differentiation factor 11 [GDF11]) that may play roles in changes in muscle mass and the aging process, however, it may be simplistic to consider aging as a result of a single peptides changes. Thus, we aimed to examine changes in activin family members across a cohort of healthy individuals of various ages, hypothesizing that these would aid predictive models of age and functional measures of age. Healthy participants (n = 88) were recruited and resting metabolic rate, body composition, grip strength, walking speed, and circulating plasma concentrations of myostatin (total and free), activin A, follistatin‐like binding protein (FLRG), and GDF11 quantified. Simple regressions between circulating factors and chronological age, grip strength, and walking speed were examined. Multiple stepwise regressions for age, grip strength, and walking speed are also reported. Age negatively correlated with total myostatin (P = 0.032, r 2 = 0.053), grip strength positively with activin A (P = 0.046, r 2 = 0.048), whereas walking speed showed no simple regression relationships. Stepwise regressions suggested a role of total myostatin and activin A in models of age, whereas GDF11 contributed to the model of grip strength. Here we suggest a role for myostatin, activin A, and GDF11 in normal human aging that mirrors animal studies to date. Further interventional studies are required to elicitate the physiological role of these changes in the normal human aging process, and indeed if offsetting these changes can promote successful aging.