Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia

Dillon, E. Lichar; Casperson, Shanon; Durham, William J.; Randolph, Kathleen M.; Urban, Randall J.; Volpi, Elena; Ahmad, Masood; Kinsky, Michael P.; Sheffield‐Moore, Melinda

doi:10.1152/ajpregu.00211.2011

Cited by 36 publications

(30 citation statements)

References 40 publications

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“…The increase in peak intensity and AUC concomitant with a greater increase in the perfusion index (the quotient of AUC and time for FWHM) is consistent with work demonstrating changes in microvascular perfusion and volume but not microvascular blood flow after exercise (20) and with sodium nitroprusside (18). Insulin is well recognized for its capacity to stimulate blood flow and recruitment of the microvasculature (for review, see Ref.…”

supporting

confidence: 81%

Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise

Churchward‐Venne¹,

Cotie²,

MacDonald³

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Churchward-Venne TA, Cotie LM, MacDonald MJ, Mitchell CJ, Prior T, Baker SK, Phillips SM. Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise. Am J Physiol Endocrinol Metab 307: E71-E83, 2014. First published May 13, 2014; doi:10.1152/ajpendo.00096.2014.-Aging is associated with anabolic resistance, a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signaling through mTORC1. Twentyone elderly males (65-80 yr) completed acute unilateral resistance exercise prior to being assigned to ingest a high dose (45 g) of whey protein (WHEY) or a low dose (15 g) of whey protein with 10 g of citrulline (WHEY ϩ CIT) or with 10 g of nonessential amino acids (WHEY ϩ NEAA). A primed, continuous infusion of L-[ring-13 C6] phenylalanine with serial muscle biopsies was used to measure MPS and protein phosphorylation, whereas ultrasound was used to measure microvascular circulation under basal and postprandial conditions in both a rested (FED) and exercised (EX-FED) leg. Argininemia was greater in WHEY ϩ CIT vs. WHEY and WHEY ϩ NEAA from 30 to 300 min postexercise (P Ͻ 0.001), but there were no treatment differences in blood flow or microvascular perfusion (all P Ͼ 0.05). Phosphorylation of p70S6K-Thr 389 was greater in WHEY vs. WHEY ϩ NEAA (P ϭ 0.02). Postprandial MPS was greater in WHEY vs. WHEY ϩ CIT and WHEY ϩ NEAA under both FED (WHEY: ϳ128%; WHEY ϩ CIT: ϳ56%; WHEY ϩ NEAA: ϳ38%) and EX-FED (WHEY: ϳ251%; WHEY ϩ CIT: ϳ124%; WHEY ϩ NEAA: ϳ108%) conditions (P ϭ 0.003). Citrulline coingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared with nonessential amino acids. citrulline; myofibrillar protein synthesis; elderly DECLINES IN MUSCLE MASS WITH AGING are due to rates of myofibrillar protein synthesis (MPS) being less than the net rate of muscle protein breakdown (37). Aminoacidemia and physical exercise are potent anabolic stimuli that elicit the synthesis of new muscle proteins; however, aging is associated with a reduced MPS response following both hyperaminoacidemia (54) and resistance exercise (28), a phenomenon termed "anabolic resistance" (for review, see Ref. 10). Although the mechanisms underlying anabolic resistance are not fully understood, age-related impairments in blood flow may be involved (31,48,50).Aminoacidemia and insulinemia increase MPS (54), arterial blood flow (54), and muscle microvascular perfusion (52) in the young; however, these responses are blunted in the elderly (48, 54). Age-related impairments in vascular function may be...

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supporting

confidence: 81%

Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise

Churchward‐Venne¹,

Cotie²,

MacDonald³

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…2E), and despite the WP maintaining significantly raised LEU concentrations for longer than the LEAA, there was no additional stimulation of MPS with WP. On this basis, research is needed to define the effects of LEU in the context of AA requirements for muscle health in old age (7,8,15,19,46,55,58).…”

Section: Discussionmentioning

confidence: 99%

Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise

Bukhari

Phillips

Wilkinson

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

128

133

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PJ. Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise. Am J Physiol Endocrinol Metab 308: E1056-E1065, 2015. First published March 31, 2015; doi:10.1152/ajpendo.00481.2014.-Dysregulated anabolic responses to nutrition/exercise may contribute to sarcopenia; however, these characteristics are poorly defined in female populations. We determined the effects of two feeding regimes in older women (66 Ϯ 2.5 yr; n ϭ 8/group): bolus whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) [LEAA; 3 g (40% leucine)]. Using [ 13 C6]phenylalanine infusions, we quantified muscle (MPS) and albumin (APS) protein synthesis at baseline and in response to both feeding (FED) and feeding plus exercise (FED-EX; 6 ϫ 8 knee extensions at 75% 1-repetition maximum). We also quantified plasma insulin/AA concentrations, whole leg (LBF)/muscle microvascular blood flow (MBF), and muscle anabolic signaling by phosphoimmunoblotting. Plasma insulinemia and EAA/aemia were markedly greater after WP than LEAA (P Ͻ 0.001). Neither LEAA nor WP modified LBF in response to FED or FED-EX, whereas MBF increased to a similar extent in both groups only after FED-EX (P Ͻ 0.05). In response to FED, both WP and LEAA equally stimulated MPS 0 -2 h (P Ͻ 0.05), abating thereafter (0 -4 h, P Ͼ 0.05). In contrast, after FED-EX, MPS increased at 0 -2 h and remained elevated at 0 -4 h (P Ͻ 0.05) with both WP and LEAA. No anabolic signals quantifiably increased after FED, but p70 S6K1 Thr 389 increased after FED-EX (2 h, P Ͻ 0.05). APS increased similarly after WP and LEAA. Older women remain subtly responsive to nutrition Ϯ exercise. Intriguingly though, bolus WP offers no trophic advantage over LEAA. skeletal muscle; blood flow; protein synthesis; aging; amino acids; exercise ILL HEALTH ASSOCIATED WITH AGING represents a major socioeconomic burden, especially given shifting demographics toward a more aged, populous world. In particular, the loss of skeletal muscle mass associated with aging, or sarcopenia, is a major clinical issue. For instance, not only are there established links between low muscle mass and all-cause mortality per se (1), but also, lower skeletal muscle mass associated with sarcopenia leads to increased frailty, risk of falls, sedentarism, poor quality of life, and prevalence of metabolic comorbidities (17, 53).The two major extrinsic influences over muscle mass are nutrition and physical activity. For example, oral intake of protein-based foods containing essential amino acids (EAA) leads to a transient (2-3 h; see Ref.2) stimulation of muscle protein synthesis (MPS) in younger men. This brief increase in MPS above postabsorptive rates serves the purpose of replenishing protein stores lost during fasting, ensuring preservation of muscle protein mass. Similarly, physical activity is a prerequisite for maintenance of a healthy muscle mass. For example, inactivity (6, 20) causes muscle atrophy by inducing "anabo...

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“…These findings suggest that attenuation of insulin-induced vasodilation in elderly people may be involved in anabolic resistance. Indeed, sodium nitroprusside, a vasodilatory NO donor, ameliorates the muscle protein anabolic effect and net balance induced by insulin or amino acids in older adults 70,71) . Also, a previous study showed that the amino acid concentration in plasma is more important for mediating protein synthesis than the intramuscular concentration 72) .…”

Section: Effect Of Blood Flow Volume On Skeletal Muscle Protein Metabmentioning

confidence: 99%

Link between blood flow and muscle protein metabolism in elderly adults

Zempo

Isobe

Naito

2017

JPFSM

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The mechanism which causes sarcopenia, a loss of muscle mass and strength with aging, remains unclear. Muscle mass is controlled by the net balance between protein synthesis and breakdown; however, net balance differences in the basal state do not contribute to sarcopenia. On the other hand, anabolic resistance, a reduction in muscle protein synthesis in response to protein intake, does seem to be involved in sarcopenia. Muscles which are subject to anabolic resistance do not show incremental blood flow volume during the fed-state. Because the vascular system transports amino acids and other nutrients that are essential for muscle protein synthesis, blood flow volume may be a regulator of anabolic resistance. There is some evidence of a link between blood flow and muscle protein metabolism. In addition, a combination of resistance training and amino acid supplementation promotes a positive net protein balance. Resistance training improves, and detraining reduces blood flow volume; therefore, blood flow volume may be involved as a background mechanism for sarcopenia. Moreover, previous studies have shown that sodium nitroprusside, a vasodilatory nitric oxide donor, enhances muscle protein synthesis. Conversely, angiotensin II, a major vasoconstrictive peptide, induces skeletal muscle protein breakdown. In this review, we discuss a possible role for blood flow in skeletal muscle protein metabolism in elderly adults. The regulation of blood flow may prove to be a beneficial treatment for sarcopenia.

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Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia

Cited by 36 publications

References 40 publications

Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise

Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise

Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise

Link between blood flow and muscle protein metabolism in elderly adults

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