rather than a simple increase in protein intake in older persons subjects since it may be difficult to achieve a high amount of dietary protein in this population. Nevertheless, according to a recent study in community‐dwelling older people, the protein pulse feeding does not induce any better effect on muscle strength, physical function, or quality of life than protein spread diet [79].
Improvement of protein retention by amino acids?
Animal and human studies have focused on the potential mechanism of the decreased skeletal muscle sensitivity to amino acids in older individuals. A defect in branched chain amino acid (BCAA) pathway activation may be responsible for this alteration [8]. Consequently, the alteration of muscle protein synthesis response to anabolic signals may be counteracted by nutritional strategies aiming at improving BCAA availability. For example, in vitro or in vivo high leucine administration is able to stimulate muscle protein synthesis rate in aged rodents [21, 80, 81]. In these models, leucine acts as an actual mediator able to drive specific intracellular pathways linked with the stimulation of protein translation [82]. Interestingly, when given to old rats for 10 days, the beneficial effect of leucine supplementation persisted, indicating that a long‐term utilization of leucine‐enriched diets may limit muscle wasting in aged individuals [83]. In addition, these data suggest that nutritional manipulations increasing the availability of leucine into skeletal muscle, such as the utilization of a leucine‐rich fast protein, i.e. whey protein, could be beneficial to improve protein retention during aging. The beneficial effect of such a diet on muscle protein synthesis in aged humans has been determined in several studies [68, 84–86]. It is concluded that leucine is able to stimulate muscle protein synthesis in the short term but may not on a longer term [87].
Special attention has also been focused on the impact of citrulline on muscle protein synthesis. This AA is not incorporated in the protein matrix during protein synthesis but it has been shown to stimulate muscle protein synthesis in malnourished animals [88]. Other amino acids, like glutamine, may be helpful to preserve skeletal muscle in older persons, especially in stressed conditions [89].
ANABOLIC RESPONSE TO PHYSICAL EXERCISE IN OLDER PERSONS
The anabolic effect of resistance exercise should be used to amplify the anabolic action of dietary proteins on muscle protein synthesis. Yarasheski et al. determined the rate of vastus lateralis muscle protein synthesis by using the in vivo incorporation of intravenously infused 13C‐leucine into mixed muscle protein in both young and older men before and at the end of two weeks of resistance exercise training [90]. Although the muscle fractional synthesis rate was lower in older persons before training, it increased to reach a comparable rate irrespective of the age of the subjects after two weeks of exercise. In contrast to these results, Welle et al. found no improvement in myofibrillar protein synthesis rate in either young or old men who completed 12 weeks of resistance training [91]. The discrepancy between these observations could be explained by the different experimental designs used in these studies. The training stimulus may not have been powerful enough to affect protein turnover in the investigation by Welle et al. [91]. In addition, the timings of muscle protein synthesis determination relative to the last bout of exercise were also different in these investigations. Further, other measurements of synthesis rate of individual muscle proteins showed that a two‐week weightlifting program increased MHC synthesis rate in 23–32 and 78‐ to 84‐year‐old subjects [92]. However, the protein synthesis rate of actin was increased after exercise only in the younger group, showing that the anabolic effect of resistance exercise in older persons is protein‐dependent. Age‐related lowering of the transcript levels of MHC IIa and IIx is not reversed by three months of resistance exercise training [93], whereas exercise resulted in a higher synthesis rate of MHC in association with an increase in MHC I isoform transcript levels [94]. Other results showed that the stimulation of MHC synthesis rate by resistance exercise is mediated by more efficient translation of mRNA [95]. Furthermore, the effect of a 16 weeks endurance exercise session on MHC isoform protein composition and mRNA abundance was tested [96]. The regulation of MHC isoform transcripts remained robust in older muscle after endurance exercise, but this did not result in corresponding changes in MHC protein expression [96].
Few data are currently available concerning the rate of muscle protein breakdown after exercise in older people. A session of 45 minutes of eccentric exercise produced a similar increase in whole body protein breakdown irrespective of the age of the subjects [97]. However, myofibrillar proteolysis, based on 3‐methylhistidine (3‐MH)/creatinine measurements, did not increase until 10 days post‐exercise in the young group but remained high through the same period in the older men [97]. In addition, the urinary 3‐MH‐to‐creatinine ratio was not affected at the end of two weeks of resistance exercise in either the younger or older volunteers [92].
Moreover, the increasing frequency of brief bouts of muscle disuse often experienced with advancing age (e.g. owing to being hospitalized, injured, or confined to the home due to adverse weather conditions) has been postulated as a contributing factor to the sarcopenic process [50]. It has been illustrated in young adults in which just five days of muscle disuse impairs the ability of skeletal muscle tissue to utilize dietary protein‐derived amino acids for de novo muscle protein synthesis [9]. In contrast, resistance‐type exercise enhances the anabolic response of skeletal muscle to nutrients, improving the capacity of skeletal muscle tissue to use dietary protein‐derived amino acids for de novo muscle protein synthesis in young and older adults [98].
From this section, it may be concluded that aging muscle still responds to exercise but there are no clear‐cut recommendations for any specific type of physical activity.
COMBINATION OF NUTRITIONAL AND TRAINING STRATEGIES
Most of the studies failed to show any beneficial effect of nutritional supplementations on muscle anabolic properties in exercising older persons. For example, Welle et al. reported that high‐protein meals (0.6–2.4 g protein/kg/d) did not enhance the myofibrillar protein synthesis rate in vastus lateralis muscle following three sessions of resistance exercise in 62‐ to 75‐year‐old men and women [99]. In very old frail people (87 years old), high‐intensity resistance exercise training with or without concomitant multinutrient supplementation had the same efficiency on muscle weakness reversibility [99]. Of note, reports showed that ingestion of oral pre‐ or post‐exercise amino acid supplements can improve net muscle protein balance in young subjects [100, 101]. The response to amino acid intake with concomitant exercise is dependent upon the composition and amount, as well as the pattern and timing of amino acid ingestion in relation to the performance of exercise [102]. The response of net muscle protein synthesis to consumption of an EAA–carbohydrate supplement solution immediately before resistance exercise is greater than when the solution is consumed after exercise, primarily because of an increase in muscle protein synthesis as a result of increased delivery of amino acids to the leg [103]. Whether amino acid and carbohydrate intakes immediately before or after resistance exercise can enhance the anabolic effect of training in older individuals as shown in the younger group is still controversial. It was shown that dietary protein digestion and absorption kinetics were not impaired after exercise at an older age. Moreover, exercising before protein intake allows for a greater use of dietary protein‐derived amino acids for de novo muscle protein synthesis in both young and older men, likely contributing to improve muscle function [98]. We investigated changes in muscle strength and fatigue of 60‐year‐old men following a 16‐week multicomponent exercise training program combined with whey proteins or total milk proteins supplementation [73]. We observed significant increases in muscle mass and strength and a reduction in muscle fatigue following training coupled with the daily consumption of 10 g of whey proteins, as compared with total milk proteins, in these subjects. Obviously, it is most important to optimize the anabolic response to resistance exercise in these participants with the aim of preserving muscle mass and function. As people are considered to prefer well‐known nutrient products that are accessible and palatable, the recommendation of exercise‐timed soluble milk protein consumption appears to be especially well suited to
