Preserving skeletal muscle mass and functional capacity is essential for healthy ageing. Transient periods of disuse and/or inactivity in combination with sub-optimal dietary intake have been shown to accelerate the age-related loss of muscle mass and strength, predisposing to disability and metabolic disease. Mechanisms underlying disuse and/or inactivity-related muscle deterioration in the older adults, whilst multifaceted, ultimately manifest in an imbalance between rates of muscle protein synthesis and breakdown, resulting in net muscle loss. To date, the most potent intervention to mitigate disuse-induced muscle deterioration is mechanical loading in the form of resistance exercise. However, the feasibility of older individuals performing resistance exercise during disuse and inactivity has been questioned, particularly as illness and injury may affect adherence and safety, as well as accessibility to appropriate equipment and physical therapists. Therefore, optimising nutritional intake during disuse events, through the introduction of protein-rich whole-foods, isolated proteins and nutrient compounds with purported pro-anabolic and anti-catabolic properties could offset impairments in muscle protein turnover and, ultimately, the degree of muscle atrophy and recovery upon re-ambulation. The current review therefore aims to provide an overview of nutritional countermeasures to disuse atrophy and anabolic resistance in older individuals.

Background Unavoidable periods of disuse lead to muscle atrophy and functional decline. Preventing such declines can reduce the risk of re-injury and improve recovery of normal physiological functioning. Objectives We aimed to determine the effectiveness of high-dose leucine supplementation on muscle morphology and strength during 7 d of unilateral lower-limb immobilization, and the role of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in disuse atrophy. Methods Sixteen healthy males (mean ± SEM age: 23 ± 1 y) underwent 7 d of unilateral lower-limb immobilization, with thrice-daily leucine (LEU; n = 8) or placebo (PLA; n = 8) supplementation (15 g/d). Before and after immobilization, muscle strength and compartmental tissue composition were assessed. A primed continuous infusion of l-[ring-13C6]-phenylalanine with serial muscle biopsies was used to determine postabsorptive and postprandial (20 g milk protein) MyoPS and MitoPS, fiber morphology, markers of protein turnover, and mitochondrial function between the control leg (CTL) and the immobilized leg (IMB). Results Leg fat-free mass was reduced in IMB (mean ± SEM: −3.6% ± 0.5%; P = 0.030) but not CTL with no difference between supplementation groups. Isometric knee extensor strength declined to a greater extent in IMB (−27.9% ± 4.4%) than in CTL (−14.3% ± 4.4%; P = 0.043) with no difference between groups. In response to 20 g milk protein, postprandial MyoPS rates were significantly lower in IMB than in CTL (−22% ± 4%; P < 0.01) in both LEU and PLA. Postabsorptive MyoPS rates did not differ between legs or groups. Postabsorptive MitoPS rates were significantly lower in IMB than in CTL (−14% ± 5%; P < 0.01) and postprandial MitoPS rates significantly declined in response to 20 g milk protein ingestion (CTL: −10% ± 8%; IMB: −15% ± 10%; P = 0.039), with no differences between legs or groups. There were no significant differences in measures of mitochondrial respiration between legs, but peroxisome proliferator–activated receptor γ coactivator 1-α and oxidative phosphorylation complex II and III were significantly lower in IMB than in CTL (P < 0.05), with no differences between groups. Conclusions High-dose leucine supplementation (15 g/d) does not appear to attenuate any functional declines associated with 7 d of limb immobilization in young, healthy males. This trial was registered at clinicaltrials.gov as NCT03762278.

In vitro models of muscle ageing are useful for understanding mechanisms of age-related muscle loss and aiding the development of targeted therapies. To investigate mechanisms of age-related muscle loss in vitro utilizing ex vivo human serum, fasted blood samples were obtained from 4 old (72 ± 1 years) and 4 young (26 ± 3 years) men. Older individuals had elevated levels of plasma CRP, IL-6, HOMA-IR, and lower concentric peak torque and work-per-repetition compared with young participants (P < 0.05). C2C12 myotubes were serum and amino acid starved for 1-hour and conditioned with human serum (10%) for 4 or 24-hours. After 4-hours C2C12 cells were treated with 5mM leucine for 30-minutes. Muscle protein synthesis (MPS) was determined through the surface sensing of translation (SUnSET) technique and regulatory signaling pathways measured via Western Blot. Myotube diameter was significantly reduced in myotubes treated with serum from old, in comparison to young donors (84%, P < 0.001). MPS was reduced in myotubes treated with old donor serum, compared to young serum prior to leucine treatment (32%, P < 0.01). MPS and the phosphorylation of Akt, p70S6K and eEF2 were increased in myotubes treated with young serum in response to leucine treatment, with a blunted response identified in cells treated with old serum (P < 0.05). Muscle protein breakdown signaling pathways did not differ between groups. In summary, we show that myotubes conditioned with serum from older individuals had decreased myotube diameter and MPS compared with younger individuals, potentially driven by low-grade systemic inflammation.