Changing demographics make it ever more important to understand the modifiable risk factors for disability and loss of independence with advancing age. For more than two decades there has been increasing interest in the role of sarcopenia, the age-related loss of muscle or lean mass, in curtailing active and healthy aging. There is now evidence to suggest that lack of strength, or dynapenia, is a more constant factor in compromised wellbeing in old age and it is apparent that the decline in muscle mass and the decline in strength can take quite different trajectories. This demands recognition of the concept of muscle quality; that is the force generating per capacity per unit cross-sectional area (CSA). An understanding of the impact of aging on skeletal muscle will require attention to both the changes in muscle size and the changes in muscle quality. The aim of this review is to present current knowledge of the decline in human muscle mass and strength with advancing age and the associated risk to health and survival and to review the underlying changes in muscle characteristics and the etiology of sarcopenia. Cross-sectional studies comparing young (18–45 years) and old (>65 years) samples show dramatic variation based on the technique used and population studied. The median of values of rate of loss reported across studies is 0.47% per year in men and 0.37% per year in women. Longitudinal studies show that in people aged 75 years, muscle mass is lost at a rate of 0.64–0.70% per year in women and 0.80–00.98% per year in men. Strength is lost more rapidly. Longitudinal studies show that at age 75 years, strength is lost at a rate of 3–4% per year in men and 2.5–3% per year in women. Studies that assessed changes in mass and strength in the same sample report a loss of strength 2–5 times faster than loss of mass. Loss of strength is a more consistent risk for disability and death than is loss of muscle mass.

We investigated how myofibrillar protein synthesis (MPS) and muscle anabolic signalling were affected by resistance exercise at 20-90% of 1 repetition maximum (1 RM) in two groups (25 each) of post-absorptive, healthy, young (24 ± 6 years) and old (70 ± 5 years) men with identical body mass indices (24 ± 2 kg m −2 ). We hypothesized that, in response to exercise, anabolic signalling molecule phosphorylation and MPS would be modified in a dose-dependant fashion, but to a lesser extent in older men. Vastus lateralis muscle was sampled before, immediately after, and 1, 2 and 4 h post-exercise. MPS was measured by incorporation of [1,2-13 C] leucine (gas chromatography-combustion-mass spectrometry using plasma [1,2-13 C]α-ketoisocaparoate as surrogate precursor); the phosphorylation of p70 ribosomal S6 kinase (p70s6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) was measured using Western analysis with anti-phosphoantibodies. In each group, there was a sigmoidal dose-response relationship between MPS at 1-2 h post-exercise and exercise intensity, which was blunted (P < 0.05) in the older men. At all intensities, MPS fell in both groups to near-basal values by 2-4 h post-exercise. The phosphorylation of p70s6K and 4EBP1 at 60-90% 1 RM was blunted in older men. At 1 h post-exercise at 60-90% 1 RM, p70s6K phosphorylation predicted the rate of MPS at 1-2 h post-exercise in the young but not in the old. The results suggest that in the post-absorptive state: (i) MPS is dose dependant on intensity rising to a plateau at 60-90% 1 RM; (ii) older men show anabolic resistance of signalling and MPS to resistance exercise.

Key points• The branched-chain amino acid (BCAA) leucine acts as both a 'trigger' for the initiation of protein synthesis, and as a substrate for newly synthesized protein.• As a BCAA, leucine can be metabolized within skeletal muscle, leaving open the possibility that leucine metabolites might possess anabolic properties.• One metabolite in particular, β-hydroxy-β-methylbutyrate (HMB), has shown positive effects on lean body mass and strength following exercise, and in disease-related muscle wasting, yet its impact on acute human muscle protein turnover is undefined.• We report here that HMB stimulates muscle protein synthesis to a similar extent to leucine.HMB was also found to decrease muscle protein breakdown.• Our observation that HMB enhances muscle protein anabolism may partly (or wholly) underlie its pre-defined anabolic/anti-catabolic supplemental efficacy in humans.Abstract Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is 'sensed' have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-13 C 2 ]Leu and [ 2 H 5 ]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A-V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70% vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling ≤90 min vs. ≤30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; −57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.

Aim We investigated architectural, functional and molecular responses of human skeletal muscle to concentric (CON) or eccentric (ECC) resistance training (RT). Methods Twelve young males performed 10 weeks of concentric (CON) or eccentric (ECC) resistance training (RT) (n = 6 CON, 6 ECC). An additional 14 males were recruited to evaluate acute muscle fascicle behaviour and molecular signalling in biopsies collected from vastus lateralis (VL) after 30 min of single bouts of CON or ECC exercise. VL volume was measured by magnetic resonance imaging. Muscle architecture (fascicle length, Lf; pennation angle, PA) was evaluated by ultrasonography. Muscle remodelling signals to CON or ECC loading [MAPK/AKT‐mammalian target of rapamycin (mTOR) signalling] and inflammatory pathway (TNFαMurf‐1‐MAFbx) were evaluated by immunoblotting. Results Despite the ~1.2‐fold greater load of the ECC group, similar increases in muscle volume (+8% CON and +6% ECC) and in maximal voluntary isometric contraction (+9% CON and +11% ECC) were found after RT. However, increases in Lf were greater after ECC than CON (+12 vs. +5%) while increases in PA were greater in CON than ECC (+30 vs. +5%). Distinct architectural adaptations were associated with preferential growth in the distal regions of VL for ECC (+ECC +8% vs. +CON +2) and mid belly for CON (ECC +7 vs. CON +11%). While MAPK activation (p38MAPK, ERK1/2, p90RSK) was specific to ECC, neither mode affected AKT‐mTOR or inflammatory signalling 30 min after exercise. Conclusion Muscle growth with CON and ECC RT occurs with different morphological adaptations reflecting distinct fibre fascicle behaviour and molecular responses.

Sarcopenia, as a marker of frailty, is an important risk factor in surgical patients but difficult to estimate using bedside testing. CT scans, performed for preoperative staging, provide an opportunity to quantify lean muscle mass without additional cost or exposure to radiation and eliminate the inconvenience of further investigations.