Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. In addition, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.

Context A diminished muscle anabolic response to protein nutrition may underpin age-associated muscle loss. Objective To determine how chronological and biological aging influence myofibrillar protein synthesis (MyoPS). Design Cross-sectional comparison. Setting Clinical research facility. Participants Ten older lean [OL: 71.7 ± 6 years; body mass index (BMI) ≤25 kg ⋅ m⁻²], 7 older obese (OO: 69.1 ± 2 years; BMI ≥30 kg ⋅ m⁻²), and 18 young lean (YL) individuals (25.5 ± 4 years; BMI ≤25 kg ⋅ m⁻²). Intervention Skeletal muscle biopsies obtained during a primed-continuous infusion of l-[ring-¹³C₆]-phenylalanine. Main Outcome Measures Anthropometrics, insulin resistance, inflammatory markers, habitual diet, physical activity, MyoPS rates, and fiber-type characteristics. Results Fat mass, insulin resistance, inflammation, and type II fiber intramyocellular lipid were greater, and daily step count lower, in OO compared with YL and OL. Postprandial MyoPS rates rose above postabsorptive values by ∼81% in YL (P < 0.001), ∼38% in OL (P = 0.002, not different from YL), and ∼9% in OO (P = 0.11). Delta change in postprandial MyoPS from postabsorptive values was greater in YL compared with OL (P = 0.032) and OO (P < 0.001). Absolute postprandial MyoPS rates and delta postprandial MyoPS change were associated with step count (r² = 0.33; P = 0.015) and leg fat mass (r² = 0.4; P = 0.006), respectively, in older individuals. Paradoxically, lean mass was similar between groups, and muscle fiber area was greater in OO vs OL (P = 0.002). Conclusion Age-related muscle anabolic resistance is exacerbated in obese inactive individuals, with no apparent detriment to muscle mass.

Skeletal muscle plays an indispensable role in metabolic health and physical function. A decrease in muscle mass and function with advancing age exacerbates the likelihood of mobility impairments, disease development, and early mortality. Therefore, the development of non-pharmacological interventions to counteract sarcopenia warrant significant attention. Currently, resistance training provides the most effective, low cost means by which to prevent sarcopenia progression and improve multiple aspects of overall health. Importantly, the impact of resistance training on skeletal muscle mass may be augmented by specific dietary components (i.e., protein), feeding strategies (i.e., timing, per-meal doses of specific macronutrients) and nutritional supplements (e.g., creatine, vitamin-D, omega-3 polyunsaturated fatty acids etc.). The purpose of this review is to provide an up-to-date, evidence-based account of nutritional strategies to enhance resistance training-induced adaptations in an attempt to combat age-related muscle mass loss. In addition, we provide insight on how to incorporate the aforementioned nutritional strategies that may support the growth or maintenance of skeletal muscle and subsequently extend the healthspan of older individuals.

Low energy availability (LEA) describes a state where the energy intake is insufficient to cover the energy costs of both exercise energy expenditure and basal physiological body functions. LEA has been associated with various physiological consequences, such as reproductive dysfunction. However, the effect of LEA on skeletal muscle protein synthesis in females performing exercise training is still poorly understood. We conducted a randomized controlled trial to investigate the impact of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in trained females. Thirty eumenorrheic females were matched based on training history and randomized to undergo 10 days of LEA (25 kcal · kg fat‐free mass (FFM)⁻¹ · day⁻¹) or optimal energy availability (OEA, 50 kcal · kg FFM⁻¹ · day⁻¹). Before the intervention, both groups underwent a 5‐day ‘run‐in’ period with OEA. All foods were provided throughout the experimental period with a protein content of 2.2 g kg lean mass⁻¹ · day⁻¹. A standardized, supervised combined resistance and cardiovascular exercise training programme was performed over the experimental period. Daily integrated muscle protein synthesis was measured by deuterium oxide (D₂O) consumption along with changes in body composition, resting metabolic rate, blood biomarkers and 24 h nitrogen balance. We found that LEA reduced daily integrated myofibrillar and sarcoplasmic muscle protein synthesis compared with OEA. Concomitant reductions were observed in lean mass, urinary nitrogen balance, free androgen index, thyroid hormone concentrations and resting metabolic rate following LEA. These results highlight that LEA may negatively affect skeletal muscle adaptations in females performing exercise training. image Key points: Low energy availability (LEA) with potential health and performance impairments is widespread among female athletes. We investigated the impact of 10 days of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in young, trained females. We show that LEA impairs myofibrillar and sarcoplasmic muscle protein synthesis in trained females performing exercise training. These findings suggest that LEA may have negative consequences for skeletal muscle adaptations and highlight the importance of ensuring adequate energy availability in female athletes.