Abstract
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.
Highlights
Human ageing is associated with a general decline in physiological function from the 3rd decade onwards, including a loss of muscle mass and strength (Kallman et al, 1990)
In line with our hypothesis, here we demonstrate that plasma from older individuals induces both reduced myoblasts migration and a reduced myotube diameter, both relative to those stimulated with younger plasma
The primary endocrine difference reported here between younger and older individuals was in the myostatin and growth and differentiation family member 11 (GDF11) inhibitor FLRG, it is of interest to note that circulating FLRG concentration in vivo correlated with the individual myotube diameter response in vitro
Summary
Human ageing is associated with a general decline in physiological function from the 3rd decade onwards, including a loss of muscle mass and strength (Kallman et al, 1990). Western society is Plasma Age Modulates Myocyte Growth experiencing an ageing population, with an increasing proportion of society >65 years of age, and an increasing need for understanding and treatment of the ageing-related loss of muscle mass and function (Bloom et al, 2015) This loss of muscle function does not result in muscle tissue losing its plasticity and ability to respond to anabolic stimuli. When age-dependent satellite cell proliferation capacity is seen in mice, the provision of insulin-like growth factor (IGF) is capable of off-setting this (Chakravarthy et al, 2000). These results suggest that the muscle cells per-se maintain functionality in ageing, but the systemic environment may instead be key
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