Exercise intensity matters for both young and old muscles

The force-producing capability of skeletal muscle allows for locomotion and the successful performance of activities of daily living. Metabolically speaking, muscle is a significant contributor to the basal metabolic rate, is the prime storage depot for body amino acids, and is a key metabolic tissue involved in glucose disposal and lipid oxidation. As such, increasing or maintaining skeletal muscle mass can decrease the risk for metabolic disorders (e.g. type 2 diabetes) as well as all-cause mortality in a variety of diseased states. A gradual decline in muscle mass and strength, termed sarcopenia, appears to be an unavoidable consequence of ageing that is associated with an increased risk for falls and the development of disorders of metabolism. Thus, studies investigating factors involved in the regulation of muscle protein turnover, with special emphasis on maintaining and even accruing lean mass, are indispensible. These studies will provide the knowledge necessary to help individuals maintain a critical level of muscle mass for overall health and well-being across the lifespan.

It is well established that resistance exercise training increases muscle strength and mass in young individuals and is also an effective countermeasure to offset the sarcopenia of ageing. The means by which resistance exercise enhances skeletal muscle mass with training is primarily through the stimulation of muscle protein synthesis. Despite the fact that resistance exercise provides the stimulus for the enhancement of muscle strength and size and is prescribed for the proper maintenance of muscle mass in all ages, we remain largely ignorant of the effect that exercise intensity has on the acute stimulation of muscle protein synthesis. In a recent issue of The Journal of PhysiologyKumar et al. (2009) are the first to systematically investigate how contraction intensity affects myofibrillar protein synthesis as well as the activation of signalling molecules involved in the regulation of mRNA translation in both young (∼24 years) and healthy elderly (∼70 years) individuals. Participants in this study were assigned to exercise at one of five different exercise intensities corresponding to 20, 40, 60, 75, or 90% of their maximal strength (1 repetition maximum; RM). The number of repetitions performed in each of the conditions was manipulated to ensure that external mechanical work was similar across the different intensities. Muscle biopsies were taken every 1–2 h to provide the time resolution necessary to accurately measure changes in the phosphorylation status of the downstream proteins of the mammalian target of rapamycin (mTOR) signalling cascade and their effect on myofibrillar protein synthesis.

The authors found that, regardless of age, an exercise intensity of at least 60% 1RM was required to elicit a significant increase in myofibrillar protein synthesis. This is in general agreement with the observation that increases in muscle hypertrophy and strength with resistance training are greater with higher exercise intensities (Holm et al. 2008). More importantly, there was no additional benefit of performing exercise at intensities greater than 60% 1RM insofar as the stimulation of myofibrillar protein synthesis was concerned (Kumar et al. 2009). These data appear to support the thesis that lifting large external loads that are close to the limits of maximal strength are apparently not necessary to maximally stimulate muscle protein synthesis. We propose that these data may aid in the development of therapeutic interventions designed to maintain and even enhance skeletal muscle mass while at the same time minimize the risk of musculoskeletal injuries in health-compromised populations such as the frail elderly, individuals with arthritis, or rehabilitation patients.

The observation that exercise intensities less than 60% 1RM are unable to substantially stimulate myofibrillar protein synthesis could be interpreted to reflect the requirement for larger mechanical strains to induce adaptive remodelling of skeletal muscle. However, muscle motor unit activation occurs in accordance with the size principle of recruitment whereby smaller motor units that typically innervate the less fatigable type I muscle fibres are activated with low effort activities (e.g. lower percentages of 1RM) whereas larger motor units that primarily innervate the greater force-generating type II fibres are recruited with higher effort activities (e.g. higher percentage of 1RM or with fatigue). The stimulation of myofibrillar protein synthesis at higher exercise intensities in the study by Kumar et al. (2009) may have simply been related to a greater recruitment of the training-responsive type II muscle fibres with the exercise stimulus. By matching total work between the conditions it is unlikely that the type II fibres, which generally exhibit a greater hypertrophic response than type I fibres, would have been activated at the lower exercise intensities resulting in a smaller protein synthetic response. For instance, performing a bout of low-intensity (20% 1RM) resistance exercise with vascular occlusion, which accelerates local metabolically induced fatigue and hastens the recruitment of type II muscle fibres to maintain work output, has been demonstrated to elicit an increase in muscle protein synthesis and phosphorylation of ribosomal protein S6 kinase 1 (S6K1) (Fujita et al. 2007a). These data could suggest that the recruitment of the type II fibres with exercise may be a more important variable in determining the extent of myofibrillar protein synthesis rather than absolute tension placed on the muscle. Future studies could manipulate exercise variables such as time under tension or exercise to failure to identify whether the recruitment of type II fibres per se has an effect on skeletal muscle protein synthesis.

Mechanistically, the stimulation of myofibrillar protein synthesis was preceded by an enhanced phosphorylation of the downstream effectors of mTOR signalling including S6K1 and 4E-binding protein (BP)1 but not eukaryotic elongation factor 2 (eEF2) suggesting changes in protein synthesis after exercise in the fasted state occur primarily via an enhanced initiation rather than elongation of mRNA translation (Kumar et al. 2009). Interestingly, there was a significant correlation between the phosphorylation, and presumably activity, of S6K1 and the rate of myofibrillar protein synthesis after exercise in the young. As the authors outline, this is the first study to identify a correlative link between S6K1 and muscle protein synthesis in humans that corroborates earlier work performed in rats and contributes to the evidence that the activation of this signalling molecule is crucial to maximizing the anabolic effect of resistance exercise (Kumar et al. 2009). The relationship between S6K1 phosphorylation and the rate of muscle protein synthesis highlights the potential usefulness of this target protein in predicting the hypertrophic potential of an exercise intervention in the young.

The authors also noted that elderly muscle was relatively resistant to the anabolic effect of resistance exercise in the fasted state demonstrating a reduced protein synthetic response at all intensities studied (Kumar et al. 2009). This may have been related in part to a relative inability to activate signalling molecules involved in the translation of mRNA such as S6K1 and 4E-BP1 (Kumar et al. 2009). Despite an attenuation in the exercise-induced rise in myofibrillar protein synthesis, suggestive of a reduced hypertrophic potential in the elderly, this exercise is probably not without its health benefits for this population. For instance, the elderly have been shown to display an anabolic resistance to nutrients at rest that may contribute to the gradual loss of muscle with ageing (Cuthbertson et al. 2005). However, resistance training improves nitrogen retention and the efficiency of dietary protein utilization in older individuals (Campbell et al. 1995). In addition, low intensity walking has previously been shown to restore the anabolic response of muscle to insulin in the elderly by improving, it was hypothesized, insulin-induced blood flow and muscle protein synthesis 20 h after exercise (Fujita et al. 2007b). Therefore, it is possible that the anabolic stimulus of resistance exercise, regardless of exercise intensity, may at least slow the progression of sarcopenia by improving nutrient sensitivity in aged muscle.

Interestingly, the rise in myofibrillar protein synthesis was relatively transient having returned to basal values by 4 h after exercise. The authors speculated that the volume of exercise may not have been sufficient to sustain the synthetic rate beyond the peak at 2 h (Kumar et al. 2009). However, it is also possible that since these individuals were exercising in an overnight-fasted condition that amino acid availability may have become limiting for protein synthesis. If this were the case, it would be valuable to determine whether or not providing an exogenous source of amino acids could sustain the duration of the elevation of myofibrillar protein synthesis after exercise.

In summary, the authors are to be commended for their investigation of the dose–response of muscle protein synthesis to resistance exercise. This information should prove beneficial when prescribing exercise interventions across the lifespan. Although an exercise intensity of at least 60% of maximal strength may be required to stimulate myofibrillar protein synthesis, we suggest there are no clear disadvantages to musculoskeletal health when individuals of all ages simply become more active.