Abstract
There is growing evidence that severe decline of skeletal muscle mass and function with age may be mitigated by exercise and dietary supplementation with protein and amino acid ingredient technologies. The purposes of this study were to examine the effects of the leucine catabolite, beta-hydroxy-beta-methylbutyrate (HMB), in C2C12 myoblasts and myotubes, and to investigate the effects of dietary supplementation with HMB, the amino acid β-alanine and the combination thereof, on muscle contractility in a preclinical model of pre-sarcopenia. In C2C12 myotubes, HMB enhanced sarcoplasmic reticulum (SR) calcium release beyond vehicle control in the presence of all SR agonists tested (KCl, P<0.01; caffeine, P = 0.03; ionomycin, P = 0.03). HMB also improved C2C12 myoblast viability (25 μM HMB, P = 0.03) and increased proliferation (25 μM HMB, P = 0.04; 125 μM HMB, P<0.01). Furthermore, an ex vivo muscle contractility study was performed on EDL and soleus muscle from 19 month old, male C57BL/6nTac mice. For 8 weeks, mice were fed control AIN-93M diet, diet with HMB, diet with β-alanine, or diet with HMB and β-alanine. In β-alanine fed mice, EDL muscle showed a 7% increase in maximum absolute force compared to the control diet (202 ± 3vs. 188± 5 mN, P = 0.02). At submaximal frequency of stimulation (20 Hz), EDL from mice fed HMB plus β-alanine showed an 11% increase in absolute force (88.6 ± 2.2 vs. 79.8 ± 2.4 mN, P = 0.025) and a 13% increase in specific force (12.2 ± 0.4 vs. 10.8 ± 0.4 N/cm2, P = 0.021). Also in EDL muscle, β-alanine increased the rate of force development at all frequencies tested (P<0.025), while HMB reduced the time to reach peak contractile force (TTP), with a significant effect at 80 Hz (P = 0.0156). In soleus muscle, all experimental diets were associated with a decrease in TTP, compared to control diet. Our findings highlight beneficial effects of HMB and β-alanine supplementation on skeletal muscle function in aging mice.
Highlights
Aging results in the progressive decline of many physiological processes including cognition [1], basal metabolic rate [2], cardiac output [3], pulmonary function [4] and neuromuscular activity [5]
We investigated the effects of both HMB treatment on cultured muscle cells and dietary HMB supplementation on muscle contractility in late middle-aged mice
A well characterized hallmark of aging skeletal muscle is the diminished capacity for regeneration of muscle after injury or exercise, and at least one contributing factor is the progressive loss of regeneration-associated satellite cells and myoblasts [76,77]
Summary
Aging results in the progressive decline of many physiological processes including cognition [1], basal metabolic rate [2], cardiac output [3], pulmonary function [4] and neuromuscular activity [5]. Additional factors contributing to muscle weakness include loss and dysmorphology of motor units [12], reduced myofiber cross sectional area, increased non-contractile tissue, reduced satellite cell activity [13] and altered myocellular calcium homeostasis [14,15,16,17,18]. These size-independent factors highlight the importance of maintaining muscle quality (strength per unit of muscle mass) during aging, over muscle quantity alone
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