Associating Inulin with a Pea Protein Improves Fast-Twitch Skeletal Muscle Mass and Muscle Mitochondrial Activities in Old Rats.

Aging is associated with a decline in muscle mass and function, leading to increased risk for mobility limitations and frailty. Dietary interventions incorporating specific nutrients, such as pea proteins or inulin, have shown promise in attenuating age-related muscle loss. This study aimed to investigate the effect of pea proteins given with inulin on skeletal muscle in old rats. Old male rats (20 months old) were randomly assigned to one of two diet groups for 16 weeks: a 'PEA' group receiving a pea-protein-based diet, or a 'PEA + INU' group receiving the same pea protein-based diet supplemented with inulin. Both groups showed significant postprandial stimulation of muscle p70 S6 kinase phosphorylation rate after consumption of pea proteins. However, the PEA + INU rats showed significant preservation of muscle mass with time together with decreased MuRF1 transcript levels. In addition, inulin specifically increased PGC1-α expression and key mitochondrial enzyme activities in the plantaris muscle of the old rats. These findings suggest that dietary supplementation with pea proteins in combination with inulin has the potential to attenuate age-related muscle loss. Further research is warranted to explore the underlying mechanisms and determine the optimal dosage and duration of intervention for potential translation to human studies.

Vitamin D status modulates mitochondrial oxidative capacities in skeletal muscle: role in sarcopenia.

Skeletal muscle mitochondrial function is the biggest component of whole-body energy output. Mitochondrial energy production during exercise is impaired in vitamin D-deficient subjects. In cultured myotubes, loss of vitamin D receptor (VDR) function decreases mitochondrial respiration rate and ATP production from oxidative phosphorylation. We aimed to examine the effects of vitamin D deficiency and supplementation on whole-body energy expenditure and muscle mitochondrial function in old rats, old mice, and human subjects. To gain further insight into the mechanisms involved, we used C2C12 and human muscle cells and transgenic mice with muscle-specific VDR tamoxifen-inducible deficiency. We observed that in vivo and in vitro vitamin D fluctuations changed mitochondrial biogenesis and oxidative activity in skeletal muscle. Vitamin D supplementation initiated in older people improved muscle mass and strength. We hypothesize that vitamin D supplementation is likely to help prevent not only sarcopenia but also sarcopenic obesity in vitamin D-deficient subjects.

Fast digestive proteins and sarcopenia of aging.

PURPOSE OF REVIEW: The speed of dietary protein digestion influences postprandial amino acid availability which is crucial for improving altered anabolic response of skeletal muscle one feature of sarcopenia during aging. RECENT FINDINGS: By analogy with carbohydrate and in reference to their absorption rate, dietary proteins can be classified as 'fast' or 'slow' proteins depending on matrix food structure and technological processes, which can influence amino acids availability and their subsequent metabolic actions. 'Fast' digestive proteins have been shown to stimulate muscle protein synthesis and to improve muscle function in several recent studies involving older patients. These new aspects may be applied for improving health through preservation or restoration of muscle protein mass and function in clinical situations (obesity, rheumatoid arthritis and cancer cachexia). SUMMARY: Using fast digestive proteins is of major interest to overcome 'anabolic resistance' of aging for limiting sarcopenia. Fast proteins' action on muscle anabolism may be stimulated by other nutrients like vitamin D or omega 3 fatty acids or by combination with exercise. The beneficial impact of the 'fast' protein concept beyond the amount of dietary protein on muscle preservation is a promising therapeutic perspective to improve mobility and quality of life of older patients affected with chronic disease.

Fast digestive, leucine-rich, soluble milk proteins improve muscle protein anabolism, and mitochondrial function in undernourished old rats.

SCOPE: One strategy to manage malnutrition in older patients is to increase protein and energy intake. Here, we evaluate the influence of protein quality during refeeding on improvement in muscle protein and energy metabolism. METHODS AND RESULTS: Twenty-month-old male rats (n = 40) were fed 50% of their spontaneous intake for 12 weeks to induce malnutrition, then refed ad libitum with a standard diet enriched with casein or soluble milk proteins (22%) for 4 weeks. A 13C-valine was infused to measure muscle protein synthesis and expression of MuRF1, and MAFbx was measured to evaluate muscle proteolysis. mTOR pathway activation and mitochondrial function were assessed in muscle. Malnutrition was associated with a decrease in body weight, fat mass, and lean mass, particularly muscle mass. Malnutrition decreased muscle mTOR pathway activation and protein FSR associated with increased MuRF1 mRNA levels, and decreased mitochondrial function. The refeeding period partially restored fat mass and lean mass. Unlike the casein diet, the soluble milk protein diet improved muscle protein metabolism and mitochondrial function in old malnourished rats. CONCLUSIONS: These results suggest that providing better-quality proteins during refeeding may improve efficacy of renutrition in malnourished older patients.

Vitamin D supplementation restores the blunted muscle protein synthesis response in deficient old rats through an impact on ectopic fat deposition.

We investigated the impact of vitamin D deficiency and repletion on muscle anabolism in old rats. Animals were fed a control (1 IU vitamin D3/g, ctrl, n=20) or a vitamin D-depleted diet (VDD; 0 IU, n=30) for 6 months. A subset was thereafter sacrificed in the control (ctrl6) and depleted groups (VDD6). Remaining control animals were kept for 3 additional months on the same diet (ctrl9), while a part of VDD rats continued on a depleted diet (VDD9) and another part was supplemented with vitamin D (5 IU, VDS9). The ctr16 and VDD6 rats and the ctr19, VDD9 and VDS9 rats were 21 and 24 months old, respectively. Vitamin D status, body weight and composition, muscle strength, weight and lipid content were evaluated. Muscle protein synthesis rate (fractional synthesis rate; FSR) and the activation of controlling pathways were measured. VDD reduced plasma 25(OH)-vitamin D, reaching deficiency (<25 nM), while 25(OH)-vitamin D increased to 118 nM in the VDS group (P<.0001). VDD animals gained weight (P<.05) with no corresponding changes in lean mass or muscle strength. Weight gain was associated with an increase in fat mass (+63%, P<.05), intramyocellular lipids (+75%, P<.05) and a trend toward a decreased plantaris weight (-19%, P=.12). Muscle FSR decreased by 40% in the VDD group (P<.001), but was restored by vitamin D supplementation (+70%, P<.0001). Such changes were linked to an over-phosphorylation of eIF2α. In conclusion, vitamin D deficiency in old rats increases adiposity and leads to reduced muscle protein synthesis through activation of eIF2α. These disorders are restored by vitamin D supplementation.

Whey proteins are more efficient than casein in the recovery of muscle functional properties following a casting induced muscle atrophy.

The purpose of this study was to investigate the effect of whey supplementation, as compared to the standard casein diet, on the recovery of muscle functional properties after a casting-induced immobilization period. After an initial (I0) evaluation of the contractile properties of the plantarflexors (isometric torque-frequency relationship, concentric power-velocity relationship and a fatigability test), the ankle of 20 male adult rats was immobilized by casting for 8 days. During this period, rats were fed a standard diet with 13% of casein (CAS). After cast removal, rats received either the same diet or a diet with 13% of whey proteins (WHEY). A control group (n = 10), non-immobilized but pair-fed to the two other experimental groups, was also studied and fed with the CAS diet. During the recovery period, contractile properties were evaluated 7 (R7), 21 (R21) and 42 days (R42) after cast removal. The immobilization procedure induced a homogeneous depression of average isometric force at R7 (CAS: - 19.0 ± 8.2%; WHEY: - 21.7 ± 8.4%; P<0.001) and concentric power (CAS: - 26.8 ± 16.4%, P<0.001; WHEY: - 13.5 ± 21.8%, P<0.05) as compared to I0. Conversely, no significant alteration of fatigability was observed. At R21, isometric force had fully recovered in WHEY, especially for frequencies above 50 Hz, whereas it was still significantly depressed in CAS, where complete recovery occurred only at R42. Similarly, recovery of concentric power was faster at R21 in the 500-700°/s range in the WHEY group. These results suggest that recovery kinetics varied between diets, the diet with the whey proteins promoting a faster recovery of isometric force and concentric power output as compared to the casein diet. These effects were more specifically observed at force level and movement velocities that are relevant for functional abilities, and thus natural locomotion.

Mitochondrial and sarcoplasmic proteins, but not myosin heavy chain, are sensitive to leucine supplementation in old rat skeletal muscle.

Leucine has a major anabolic impact on muscle protein synthesis in young as in old animals. However, myosin heavy chain (MHC), sarcoplasmic and mitochondrial proteins may differently respond to anabolic factors, especially during aging. To test this hypothesis, fractional synthesis rates (FSR) of the three muscle protein fractions were measured using a flooding dose of [1-(13)C] phenylalanine, in gastrocnemius muscle of adult (8 months) and old (22 months) rats, either in postabsorptive state (PA), or 90-120 min after ingestion of a alanine-supplemented meal (PP+A) or a leucine-supplemented meal (PP+L). In adult and old rats, in comparison with PA, leucine stimulated mitochondrial (adult: 0.260+/-0.011 vs 0.238+/-0.012%h(-1); old: 0.289+/-0.010 vs 0.250+/-0.010%h(-1); PP+L vs PA, P<0.05) and sarcoplasmic (adult: 0.182+/-0.011 vs 0.143+/-0.006%h(-1); old: 0.195+/-0.010 vs 0.149+/-0.008%h(-1); PP+L vs PA, P<0.05) protein FSR, but not MHC synthesis in old rats (0.101+/-0.009 vs 0.137+/-0.018%h(-1); PP+L vs PA, P=NS). In conclusion, synthesis of specific muscle protein is activated by leucine supplementation, but MHC may be less sensitive to anabolic factors with aging.