Anabolic Resistance in the Pathogenesis of Sarcopenia in the Elderly: Role of Nutrition and Exercise in Young and Old People

Abstract

The development of sarcopenia in the elderly is associated with many potential factors and/or processes that impair the renovation and maintenance of skeletal muscle mass and strength as ageing progresses. Among them, a defect by skeletal muscle to respond to anabolic stimuli is to be considered. Common anabolic stimuli/signals in skeletal muscle are hormones (insulin, growth hormones, IGF-1, androgens, and β-agonists such epinephrine), substrates (amino acids such as protein precursors on top, but also glucose and fat, as source of energy), metabolites (such as β-agonists and HMB), various biochemical/intracellular mediators), physical exercise, neurogenic and immune-modulating factors, etc. Each of them may exhibit a reduced effect upon skeletal muscle in ageing. In this article, we overview the role of anabolic signals on muscle metabolism, as well as currently available evidence of resistance, at the skeletal muscle level, to anabolic factors, from both in vitro and in vivo studies. Some indications on how to augment the effects of anabolic signals on skeletal muscle are provided.

Keywords: exercise; intracellular signals; nutrition; protein foods; protein synthesis; sarcopenia; skeletal muscle.

Figure 1

Here is a diagram showing the typical triggers for muscle growth in young people, which include exercise and high-quality protein intake. These stimuli activate various molecular pathways that lead to muscle hypertrophy. However, on the right-hand side of the diagram, you can see that the same stimuli do not have the same effect on skeletal muscle in cases of anabolic resistance.

Figure 2

The figure schematically illustrates the methodology commonly employed to determine skeletal muscle fractional protein synthesis rate (FSR) with the combined infusion of an amino acid tracer (in this example, phenylalanine, (phe)) and its timed incorporation into skeletal muscle (measured by biopsy). Absolute Muscle Protein Synthesis (MPS) rate is calculated as the product of FSR times muscle protein mass. The asterisks (*) indicate the labeled amino acid. Abbreviations used in the Figure: art: artery; m: muscle; prec.: the enrichment (or the specific activity) of the “precursor” (i.e., the labeled amino acid), used in the calculations.

Figure 3

Measurement of skeletal muscle protein synthesis and degradation with arterial/venous combined with isotope infusion. The figure schematically depicts the measurements performed in the perfusing artery and in the deep vein draining blood from the sampled muscular-rich district (i.e., the leg or the forearm). In this example, the indicator essential amino acid is phenylalanine (Phe), which is utilized by muscle only for protein synthesis and is released from muscle only from protein degradation. Blood flow across the muscle district has to be measured too. Thus, from the measured phenylalanine utilization and release, it is possible to extrapolate protein degradation and synthesis. The asterisk (*) indicates the labeled amino acid. Abbreviations used in the Figure: art: artery; ven: vein; ic: intracellular. The equations used in the calculations are not reported here.