Aging differentially affects human skeletal muscle amino acid transporter expression when essential amino acids are ingested after exercise

Dickinson, Jared M.; Drummond, Micah J.; Coben, Jennifer R.; Volpi, Elena; Rasmussen, Blake B.

doi:10.1016/j.clnu.2012.07.009

Cited by 62 publications

(65 citation statements)

References 30 publications

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“…We speculate that an acute increase in RAGB/RAGB mRNA and protein may be an adaptive response important to amplify a subsequent anabolic stimulus. These findings, coupled with our previous findings (12)(13)(14)(15), support conducting a future clinical trial to test whether a previous protein-enriched meal (i.e., breakfast) may serve as the basis for producing a magnified protein anabolic response to a second meal (i.e., lunch). Additionally, an acute upregulation of RAGB with EAA ingestion may be partly related to the additive anabolic response that is observed when EAAs are ingested in close proximity to a bout of resistance exercise (27)(28)(29).…”

Section: Discussionsupporting

confidence: 51%

“…In our previous work in human skeletal muscle, we observed repeatedly an acute upregulation of the mRNA and protein of select amino acid transporters (important regulators of mTORC1 activation) after EAA ingestion alone, after a bout of resistance exercise, and after the combination of EAA or protein ingestion immediately after resistance exercise (12)(13)(14)(15). Interestingly, these nutrient regulators had an overlapping time course response with changes in skeletal mTORC1 signaling and MPS and thus may play a role in promoting protein anabolism.…”

Section: Introductionmentioning

confidence: 83%

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Skeletal Muscle Ras-Related GTP Binding B mRNA and Protein Expression Is Increased after Essential Amino Acid Ingestion in Healthy Humans

Carlin

Tanner

Agergaard

et al. 2014

The Journal of Nutrition

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Essential amino acids (EAAs) are potent stimulators of mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis. However, regulators upstream of mTORC1 that are responsive to EAA availability are not well described, especially in human skeletal muscle. The purpose of this study was to determine changes in leucyl-tRNA synthetase (LARS/LARS) and Ras-related GTP binding B (RAGB/RAGB) mRNA and protein expression in healthy human skeletal muscle after acute EAA ingestion. Muscle biopsies sampled from the vastus lateralis were obtained from 13 young adults (7 males, 6 females; aged 22.9 ± 0.9 y; body mass index 21.7 ± 0.9 kg/m(2)) in the fasting state (baseline) and 1 and 3 h after EAA (13 g; 2.4 g of Leu) ingestion. Real-time quantitative polymerase chain reaction and Western blotting were used to determine changes in LARS/LARS and RAGB/RAGB mRNA and protein expression, respectively. Stable isotope tracers and gas chromatography mass spectrometry were used to determine Leu intracellular concentrations and muscle protein synthesis. EAA ingestion increased RAGB/RAGB mRNA (∼60%) and protein (∼100%) abundance in adult skeletal muscle (P ≤ 0.05). EAAs also increased muscle Leu concentrations (∼130%), mTOR phosphorylation (∼30%), and muscle protein synthesis (∼50%; P ≤ 0.05) but did not alter muscle LARS/LARS abundance (P > 0.05). We conclude that acute EAA ingestion is capable of increasing RAGB expression in human skeletal muscle. Future work is needed to determine whether this adaptive response is important to promote muscle protein anabolism in humans. This trial was registered at clinicaltrials.gov as NCT01669590.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 83%

Skeletal Muscle Ras-Related GTP Binding B mRNA and Protein Expression Is Increased after Essential Amino Acid Ingestion in Healthy Humans

Carlin

Tanner

Agergaard

et al. 2014

The Journal of Nutrition

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“…We observed a downregulation of the system L amino acid transporter gene SLC7A5. Although SLC7A5 mRNA has been shown to be elevated after REX alone (16) and also following REX and protein ingestion when subjects are in EB (14), our results indicate that REX undertaken in ED acts to suppress the typical exercise/nutrient-mediated upregulation of SLC7A5 mRNA abundance (Fig. 7D).…”

Section: E994mentioning

confidence: 74%

Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit

Areta

Burke²,

Camera

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

160

184

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Postabsorptive rates of MPS were 27% lower in ED than EB (P Ͻ 0.001), but REX stimulated MPS to rates equal to EB. Ingestion of 15 and 30 g of protein after REX in ED increased MPS ϳ16 and ϳ34% above resting EB (P Ͻ 0.02). p70 S6K Thr 389 phosphorylation increased above EB only with combined exercise and protein intake (ϳ2-7 fold, P Ͻ 0.05). In conclusion, short-term ED reduces postabsorptive MPS; however, a bout of REX in ED restores MPS to values observed at rest in EB. The ingestion of protein after REX further increases MPS above resting EB in a dose-dependent manner. We conclude that combining REX with increased protein availability after exercise enhances rates of skeletal muscle protein synthesis during short-term ED and could in the long term preserve muscle mass. body composition; fat-free mass; myofibrillar protein synthesis; weight loss ENERGY DEFICIT (ED) can be achieved through reduced energy intake and/or increased energy expenditure and subsequently leads to loss of fat mass (FM). A reduction in FM is a goal for improved health (19, 33); however, when achieved by energy restriction alone, it typically results in the concomitant weight loss comprised of ϳ25% fat-free mass (FFM) (52), of which skeletal muscle is the main component (37,39). Given that the quality and quantity of skeletal muscle is a major determinant of whole body metabolic rate and functional capacity throughout the lifespan (25), nutritional and exercise strategies to prevent or minimize loss of FFM while losing fat mass are crucial.Pasiakos et al. (41) reported a 19% reduction in basal rates of mixed-muscle protein synthesis in young healthy males and females after 10 days of ED (ϳ500 kcal/day). In contrast, a more recent study from Pasiakos et al. (40) found no decrease in rates of resting muscle protein synthesis after 30 days of moderate ED. If a potential decrease in basal rates of muscle protein synthesis was not accompanied by a concomitant reduction in muscle protein breakdown, then ED would presumably result in a marked loss of skeletal muscle protein. Indeed, prolonged ED-induced body weight loss can be comprised of up to 60% FFM (40). In contrast, exercise has been shown to attenuate the loss of lean body tissue that typically occurs with periods of ED alone (50). However, it is currently unknown whether the anabolic effects of resistance exercise (REX) are attenuated during periods of ED.Provision of dietary amino acids increases skeletal muscle protein synthesis, an effect that is enhanced by prior REX (3, 36). To date, only one study has examined whether skeletal muscle exhibits "anabolic resistance" to exercise and protein ingestion following short-term ED (40). However, in that investigation, rates of mixed-muscle protein synthesis and not myofibrillar protein synthesis (MPS; i.e., the contractile protein fraction of muscle) were measured. Furthermore, there was no examination of the impact of exercise, and the cohort under investigation was comprised mainly of males. Hence, the primary aim of the current study was...

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“…Research has begun to investigate the potential role of amino acid transporters in the anabolic response to food intake (29), given that these proteins not only play a role in the transport (both influx and efflux) of amino acids across the muscle membrane but also appear to act as a nutrient receptor [i.e., a "transceptor" (30)], the latter of which may help initiate anabolic signaling in a feed-forward manner. Limited research has revealed that basal amino acid transporter protein expression does not appear to be appreciably influenced by aging per se (31,32), although without a complete picture as to the location (e.g., intracellular vs. intramembranous) and/or functionality (i.e., transport activity/capacity) of these proteins in older muscle, their contribution to the anabolic resistance of aging cannot be ruled out. Finally, the translational machinery of older muscle may have a reduced capacity for and/or sensitivity to amino acids, as suggested by observations of a reduced ribosomal protein content (15) and/or dysregulated mTOR (or 1 of its primary downstream effectors ribosomal protein S6 kinase) signaling in response to exogenous amino acids and/or insulin in older muscle (15,33).…”

Section: Metabolic Regulation Of Skeletal Muscle Massmentioning

confidence: 92%

Keeping Older Muscle “Young” through Dietary Protein and Physical Activity

Moore

2014

Advances in Nutrition

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Sarcopenia is characterized by decreases in both muscle mass and muscle function. The loss of muscle mass, which can precede decrements in muscle function, is ultimately rooted in an imbalance between the rates of muscle protein synthesis and breakdown that favors a net negative balance (i.e., synthesis < breakdown). A preponderance of evidence highlights a blunted muscle protein synthetic response to dietary protein, commonly referred to as “anabolic resistance,” as a major underlying cause of the insipid loss of muscle with age. Dietary strategies to overcome this decreased dietary amino acid sensitivity include the ingestion of leucine-enriched, rapidly digested proteins and/or greater protein ingestion in each main meal to maximally stimulate muscle anabolism. Anabolic resistance is also a hallmark of a sedentary lifestyle at any age. Given that older adults may be more likely to experience periods of reduced activity (either voluntarily or through acute illness), it is proposed that inactivity is the precipitating factor in the development of anabolic resistance and the subsequent progression from healthy aging to frailty. However, even acute bouts of activity can restore the sensitivity of older muscle to dietary protein. Provided physical activity is incorporated into the daily routine, muscle in older adults should retain its capacity for a robust anabolic response to dietary protein comparable to that in their younger peers. Therefore, through its ability to “make nutrition better,” physical activity should be viewed as a vital component to maintaining muscle mass and function with age.

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Aging differentially affects human skeletal muscle amino acid transporter expression when essential amino acids are ingested after exercise

Cited by 62 publications

References 30 publications

Skeletal Muscle Ras-Related GTP Binding B mRNA and Protein Expression Is Increased after Essential Amino Acid Ingestion in Healthy Humans

Skeletal Muscle Ras-Related GTP Binding B mRNA and Protein Expression Is Increased after Essential Amino Acid Ingestion in Healthy Humans

Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit

Keeping Older Muscle “Young” through Dietary Protein and Physical Activity

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