Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults

Volpi, Elena; Kobayashi, Hisamine; Sheffield‐Moore, Melinda; Mittendorfer, Bettina; Wolfe, Robert R.

doi:10.1093/ajcn/78.2.250

Cited by 718 publications

(525 citation statements)

References 32 publications

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“…immediately after absorption) [34,36], this does not appear to influence the systemic amino acid concentration, which normally increases in the elderly as well as in the young, and consequently the muscle anabolic effect of amino acids [34]. EAAs, in particular, are able to stimulate muscle protein synthesis in the elderly, whereas non-EAAs do not appear to provide any additional benefit with regard to muscle protein deposition and anabolism [35]. Among the EAAs, the branched-chain amino acid (BCAA) leucine has been shown to be a key regulator of muscle protein synthesis in both humans and rats [37][38][39].…”

Section: Amino Acids and Regulation Of Muscle Metabolism In Healthy Amentioning

confidence: 99%

“…A number of studies have shown that pure amino acids can stimulate muscle protein synthesis and improve net protein balance in older as well as in younger individuals [19,[32][33][34][35]. Although older persons have an increased splanchnic extraction of orally administered amino acids at first pass (i.e.…”

Section: Amino Acids and Regulation Of Muscle Metabolism In Healthy Amentioning

confidence: 99%

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Amino acid metabolism and regulatory effects in aging

Timmerman

Volpi²

2008

Current Opinion in Clinical Nutrition and Metabolic Care

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Purpose of review-To examine recent discoveries related to the amino acid metabolism and regulatory effects in aging, focusing on the development and treatment of age-related muscle loss (sarcopenia).Recent findings-While basal amino acid metabolism may be unaffected by age, elderly subjects appear to have a decreased ability to respond to anabolic stimuli such as insulin and, to a lesser extent, amino acids. Specifically, compared to young subjects, the stimulation of muscle protein synthesis is attenuated in elderly subjects following the administration of mixed meals due to insulin resistance. In addition, the anabolic effect of amino acids appears blunted at low doses. Recent studies, however, have highlighted that these age-related alterations in amino acid metabolism may be overcome by provision of excess leucine, changes in the daily protein intake pattern or exercise, which improve activation of translation initiation and muscle protein synthesis.Summary-Muscle loss with aging is associated with significant changes in amino acid metabolism, which can be acutely reversed using nutritional manipulations and exercise. Longterm, large clinical trials are, however, needed to determine the clinical significance of these findings in the elderly population, and to establish if nutritional and exercise interventions can help prevent and treat sarcopenia.

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Section: Amino Acids and Regulation Of Muscle Metabolism In Healthy Amentioning

confidence: 99%

Section: Amino Acids and Regulation Of Muscle Metabolism In Healthy Amentioning

confidence: 99%

Amino acid metabolism and regulatory effects in aging

Timmerman

Volpi²

2008

Current Opinion in Clinical Nutrition and Metabolic Care

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“…In contrast, DR has only one principal negative effect: muscle weakness due to protein wasting (Lopes, Russell, Whitwell, & Jeejeebhoy, 1982; Thomas, 2007), which also represents a health problem in both elderly subjects and patients with kidney disease (Goodpaster et al., 2006; Workeneh & Mitch, 2010). Recently, a beneficial effect of dietary protein or amino acid supplementation on muscle weakness has been proposed (Paddon‐Jones & Rasmussen, 2009; Paddon‐Jones, Short, Campbell, Volpi, & Wolfe, 2008; Volpi, Kobayashi, Sheffield‐Moore, Mittendorfer, & Wolfe, 2003). However, there has been concern that such a supplement may adversely affect the progression of CKD and reduce DR‐induced health benefits.…”

Section: Introductionmentioning

confidence: 99%

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

et al. 2018

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SummaryExtending healthy lifespan is an emerging issue in an aging society. This study was designed to identify a dietary method of extending lifespan, promoting renoprotection, and preventing muscle weakness in aged mice, with a focus on the importance of the balance between dietary essential (EAAs) and nonessential amino acids (NEAAs) on the dietary restriction (DR)‐induced antiaging effect. Groups of aged mice were fed ad libitum, a simple DR, or a DR with recovering NEAAs or EAAs. Simple DR significantly extended lifespan and ameliorated age‐related kidney injury; however, the beneficial effects of DR were canceled by recovering dietary EAA but not NEAA. Simple DR prevented the age‐dependent decrease in slow‐twitch muscle fiber function but reduced absolute fast‐twitch muscle fiber function. DR‐induced fast‐twitch muscle fiber dysfunction was improved by recovering either dietary NEAAs or EAAs. In the ad libitum‐fed and the DR plus EAA groups, the renal content of methionine, an EAA, was significantly higher, accompanied by lower renal production of hydrogen sulfide (H2S), an endogenous antioxidant. Finally, removal of methionine from the dietary EAA supplement diminished the adverse effects of dietary EAA on lifespan and kidney injury in the diet‐restricted aged mice, which were accompanied by a recovery in H2S production capacity and lower oxidative stress. These data imply that a dietary approach could combat kidney aging and prolong lifespan, while preventing muscle weakness, and suggest that renal methionine metabolism and the trans‐sulfuration pathway could be therapeutic targets for preventing kidney aging and subsequently promoting healthy aging.

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“…mTORC1 signaling has consistently shown to be activated in response to both muscle loading (e.g., resistance exercise), and amino acid consumption/treatment (Marcotte, West, & Baar, 2015), and as such these stimuli represent excellent candidates as therapies for attenuating the muscle wasting associated with a number of disease states and ageing. Indeed, acute human studies have observed activation of mTORC1 and its downstream targets (e.g., p70S6K, rpS6, and 4EBP‐1) following ingestion of mixed amino acids, and this is coupled with an increase in muscle protein synthesis (MPS) in the ensuing 60–120 min (Atherton, Etheridge et al, 2010; Koopman et al, 2006; Paddon‐Jones et al, 2004; Volpi, Kobayashi, Sheffield‐Moore, Mittendorfer, & Wolfe, 2003). Furthermore, when human skeletal muscle undergoes loading prior to amino acid ingestion this effect on mTORC1 signaling and MPS is potentiated (Moore, Atherton, Rennie, Tarnopolsky, & Phillips, 2011; Witard et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro

Martin

Turner

Farrington

et al. 2017

Journal Cellular Physiology

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The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP‐1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co‐incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly‐controlled investigations into nutritional regulation of muscle physiology.

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Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults

Abstract: Essential amino acids are primarily responsible for the amino acid-induced stimulation of muscle protein anabolism in the elderly.

Cited by 718 publications

References 32 publications

Amino acid metabolism and regulatory effects in aging

Amino acid metabolism and regulatory effects in aging

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro

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