Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise

Abstract

Skeletal muscles comprise a substantial portion of whole body mass and are integral for locomotion and metabolic health. Increasing age is associated with declines in both muscle mass and function (e.g. strength-related performance, power) with declines in muscle function quantitatively outweighing those in muscle volume. The mechanisms behind these declines are multi-faceted involving both intrinsic age-related metabolic dysregulation and environmental influences such as nutritional and physical activity. Ageing is associated with a degree of 'anabolic resistance' to these key environmental inputs, which likely accelerates the intrinsic processes driving ageing. On this basis, strategies to sensitize and/or promote anabolic responses to nutrition and physical activity are likely to be imperative in alleviating the progression and trajectory of sarcopenia. Both resistance- and aerobic-type exercises are likely to confer functional and health benefits in older age, and a clutch of research suggests that enhancement of anabolic responsiveness to exercise and/or nutrition may be achieved by optimizing modifications of muscle-loading paradigms (workload, volume, blood flow restriction) or nutritional support (e.g. essential amino acid/leucine) patterns. Nonetheless, more work is needed in which a more holistic view in ageing studies is taken into account. This should include improved characterization of older study recruits, that is physical activity/nutritional behaviours, to limit confounding variables influencing whether findings are attributable to age, or other environmental influences. Nonetheless, on balance, ageing is associated with declines in muscle mass and function and a partially related decline in aerobic capacity. There is also good evidence that metabolic flexibility is impaired in older age.

Keywords: ageing; muscle; protein turnover; substrate metabolism.

Figure 1

Overview of signalling and muscle proteins synthesis (MPS) responses induced by amino acids (AAs) and different contraction intensities. An increase in intracellular AAs leads to the activation of the mammalian target of rapamycin (mTORC1) and its associated downstream protein substrates: 4E‐binding protein 1 (4E‐BP1) and p70 ribosomal protein S6 kinase 1 (S6K1), promoting assembly of the pre‐initiation complex and mRNA translational efficiency. AA‐induced increases in MPS are transient and return back to baseline despite elevated AAs. Exercise prior to AA availability enhances protein synthetic responses which may persist for >24 h, resulting in greater net protein accretion. Resistance exercise (RE) favours stimulation of myofibrillar (myo) MPS through activation of the mTORC1 pathway, with repeated bouts leading to accumulation of contractile proteins and muscle hypertrophy. Endurance exercise (EE) favours stimulation of mitochondrial (Mito) protein synthesis through activation of 5′ AMP‐activated protein kinase (AMPK) and stimulation of proteins involved in mitochondrial biogenesis. Repeated performance of EE increases muscle mitochondrial content increasing oxidative capacity. Phospholipase D (PLD), phosphatidic acid (PA), adenosine monophosphate (AMP), adenosine triphosphate (ATP), peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α), eukaryotic translation initiation factor 4E (eIF4E), ribosomal protein S6 (RPS6), eukaryotic elongation factor 2 (eEF2). ↑ represents activation, and Τ represents inhibition.