deficiency could exacerbate the effects of aging on muscle, i.e. sarcopenia [36]. The related lipotoxicity was shown to be detrimental for type II muscles at least, with a significant decrease in fasted muscle protein synthesis. Interestingly, vitamin D supplementation in old vitamin D‐deficient rats prevented these changes. In addition, it was recently reported that a six‐month treatment with vitamin D showed beneficial effects on appendicular muscle mass in pre‐sarcopenic older men and women [37]. With regard to the cellular mechanism, as revealed in murine C2C12 skeletal myotubes, vitamin D sensitizes the Akt/mTOR‐dependent pathway to the stimulating effect of leucine and insulin, resulting in a further activation of protein synthesis [38].
Figure 5.2 Activation of insulin signaling pathway by amino acids.
What is the basis of protein requirement during aging?
Protein requirement is defined as the lowest dietary protein intake able to compensate for the obligatory losses of nitrogen from the body and to preserve bodily functions [39]. The current mean dietary requirement for healthy adult men and women of all ages, was set by the 1985 joint FAO/WHO/UNU expert consultation, and estimated to be 0.6 g protein/kg/d, with a suggested safe level of intake set at 0.75 g protein/kg/d [40]. However, because of many changes in body organs functions and metabolism with age, such as body composition, insulin resistance, altered protein metabolism especially in skeletal muscle, some authors [41–44] have suggested that the utilization of dietary proteins and amino acids may differ between the young and the older adults. Consequently, the same authors, using various methodologies, i.e. nitrogen balance and tracer procedures, have tried to define the modifications of protein requirement with advancing age [41–44]. Taken together, studies based on nitrogen balance using the same formula, showed that protein requirement increases in older people, especially in aged individuals during compulsory inactivity such as bed rest [45].
It is generally difficult to establish firm recommendations for protein intake for this population, but it is safe to consider that protein requirement can be slightly increased in older people to limit loss of lean body mass and preserve a better response to any critical stress like sepsis or trauma. Recommendations for dietary protein intake in older persons have been reviewed in 2013 by the PROT‐AGE study group [46, 47]. According to these experts in geriatrics and nutrition, older people should consume an average daily intake of 1.0–1.2 g/kg/d in healthy condition and 1.2–1.5 g/kg/d in disease states, respectively.
This current recommendation is reflected by data from the Health ABC study showing that despite adequate intakes of dietary protein, appendicular muscle mass (reflecting whole body muscle mass) was lost during a three‐year follow‐up and that the less protein is eaten the more muscle is lost [48]. Thus, it is possible that nitrogen balance may not exactly reflect the small changes in protein metabolism that happen every day at a low scale, but cumulating for months can result in a significant decline in muscle protein mass. In this case, it is hypothesized that adaptation of older persons to protein restriction may be inadequate as already reported by Castaneda et al. [49]. This is the reason why most of the research should also focus on the incomplete recovery of muscle mass following stress also called “the catabolic crisis model” [50]. For instance in hospitalized older persons, nitrogen balance studies indicate that a daily intake of 1.3–1.6 g protein /kg/d should be applied [51].
How to improve protein retention in older persons: beyond protein quantity?
What is the response to increasing protein intakes?
Surprisingly, only a few experiments were designed to study the effect of increased or decreased protein intake in an older population. When the protein amount in the diet increases from 12 to 21% of total energy, whole body protein turnover was enhanced in older men and women [52]. Following a low protein intake (50% of usual intake), no modification of whole body protein synthesis and breakdown was noticed in a group of aged women [53]. However, whole body protein oxidation, nitrogen balance, muscle mass and function, and immune response were significantly affected in the group fed a low‐protein diet [49]. Collectively, these observations highlight the importance of maintaining adequate protein intakes in older people to counteract the negative effect of aging on protein metabolism. These previous observations were repeated indicating some adaptations using muscle‐specific transcript profiles [54]. Of course, the other important question is about the upper limit of protein intakes in older persons, knowing that a reduced glomerular filtration capacity is occurring. To address this issue, we demonstrated [55] that a high‐protein ingestion, i.e. 3 g/kg fat‐free mass/d for 10 days, was inefficient to enhance protein synthesis at whole body as well as the skeletal muscle levels in healthy older persons in the postabsorptive state. Interestingly, although a high protein diet normally enhanced glomerular filtration rate in young adults, it reduced renal function in the aged group [55]. Other data have shown long ago that the maximal adaptive capacity of ureagenesis in adults (for a mean weight of 70 kg) was about 22 mg of urea nitrogen/kg body weight/h [56]. These data correspond to a maximal protein consumption of ∼3.3 g/kg/d, so that the safe upper limit for protein intake has been fixed to less than 2.2 g/kg/d by the French group on protein recommendation for older persons [57]. In addition, reports have highlighted that the amount of protein consumed per meal is important for muscle mass and function. In fact, consuming frequent meals containing 30–45 g of protein was associated with greater leg lean mass and knee extensor muscle strength [58]. The above mentioned nutritional strategy was also associated with higher appendicular lean body mass (an index of muscle mass) in both older men and women at baseline and after a two‐year follow‐up period [59]. Besides the quantity of protein consumed, the source of protein, the quality of protein, i.e. its digestibility and its composition in EAAs, can modulate protein metabolism and be beneficial for muscle quality.
Is there an effect of the protein source?
The consumption of different protein sources and its effect on protein metabolism has been assessed in older women [60]. One diet was composed half of animal proteins and half of vegetable proteins, whereas one‐third of the proteins consumed in a second diet were from vegetable and two‐thirds from animals, and inversely in a third diet. Nitrogen balance was not modified in this study, but whole body protein breakdown was not inhibited to the same extent by the meal when the protein source was from vegetables in comparison with meat [60]. This study showed that intake of high‐quality proteins may be an important issue in older people, suggesting also that aging may be associated with more specific amino acid requirements especially for the EAAs. The quality of dietary proteins and its impact on muscle protein synthesis may be less important when protein intake is sufficient. In a previous study, we compared milk and soy proteins were compared for their potential impact on muscle protein synthesis using a classical steady‐state approach [61]. No differences could be found between the different sources of dietary proteins despite changes in leg amino acid uptakes. However, there is not enough data in the field of aging regarding the issue of EAAs especially at low protein intakes.
Several studies have evaluated the effect of consuming plant‐based proteins on muscle protein metabolism in young, adult, and old rats, pigs, and humans, compared to animal proteins, i.e., meat, milk, and its constitutive proteins (casein and whey proteins) [62]. A few of these studies have focused on the impact of plant‐based foods [60], soy protein [63, 64], or wheat protein [65] ingestion on protein synthesis at the whole body or skeletal muscle level in older individuals. The majority of these studies have reported that good‐quality animal proteins have a greater ability to enhance muscle protein synthesis rate and to support muscle mass than plant‐based proteins. Therefore, although plant‐based protein sources that are rich in fiber and micronutrients may be valuable to improve nutritional density of diet, they have lower anabolic potential than animal‐based proteins. Strategies to improve these properties by increasing protein quality (i.e., their amino acid composition and