Myofibrillar protein synthesis in young and old human subjects after three months of resistance training

Welle, Stephen; Thornton, Charles A.; Statt, Marcia

doi:10.1152/ajpendo.1995.268.3.e422

Cited by 103 publications

(109 citation statements)

References 18 publications

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“…Several researchers have reported an age-related reduction in total muscle (48), myofibrillar (11,49,50), or myosin heavy chain (51) protein synthesis rates, whereas others (52) and our laboratory (Ref. 14 and the present study) did not find any difference.…”

Section: Nih-pa Author Manuscriptcontrasting

confidence: 82%

The Response of Muscle Protein Anabolism to Combined Hyperaminoacidemia and Glucose-Induced Hyperinsulinemia Is Impaired in the Elderly

Volpi¹

2000

Journal of Clinical Endocrinology & Metabolism

324

322

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Muscle mass declines with aging. Amino acids alone stimulate muscle protein synthesis in the elderly. However, mixed nutritional supplementation failed to improve muscle mass. We hypothesized that the failure of nutritional supplements is due to altered responsiveness of muscle protein anabolism to increased amino acid availability associated with endogenous hyperinsulinemia.We measured muscle protein synthesis and breakdown, and amino acid transport in healthy young (30 ± 3 yr) and elderly (72 ± 1 yr) volunteers in the basal postabsorptive state and during the administration of an amino acid-glucose mixture, using L-[ring-2 H 5 ]phenylalanine infusion, femoral artery and vein catheterization, and muscle biopsies. Basal muscle amino acid turnover was similar in young and elderly subjects. The mixture increased phenylalanine leg delivery and transport into the muscle in both groups. Phenylalanine net balance increased in both groups (young, −27 ± 8 to 64 ± 17; elderly, −16 ± 4 to 29 ± 7 nmol/(min·100 mL); P < 0.0001, basal vs. mixture), but the increase was significantly blunted in the elderly (P = 0.030 vs. young). Muscle protein synthesis increased in the young, but remained unchanged in the elderly [young, 61 ± 17 to 133 ± 30 (P = 0.005); elderly, 62 ± 9 to 70 ± 14 nmol/(min·100 mL) (P = NS)]. In both groups, protein breakdown decreased (P = 0.012) and leg glucose uptake increased (P = 0.0258) with the mixture.We conclude that the response of muscle protein anabolism to hyperaminoacidemia with endogenous hyperinsulinemia is impaired in healthy elderly due to the unresponsiveness of protein synthesis.Muscle mass and function progressively decline with aging (1, 2). This process has been termed sarcopenia and is associated with risk of falls and functional dependence (3,4). Both undernutrition and disuse have been identified as potentially preventable contributing factors (5, 6). Nutritional intervention is an appealing method of prevention and treatment of sarcopenia of the elderly due to its wide applicability and safety. However, attempts to NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript improve muscle mass and strength in the elderly with nutritional supplements failed to demonstrate a beneficial effect (7,8).The failure of nutritional supplementation in the treatment of sarcopenia of the elderly may be due to age-related alterations of muscle protein metabolism in response to feeding. This hypothesis is indirectly supported by recent data in humans suggesting that protein requirements increase with age (9). Increased protein requirements in aging suggest a decline in the ability of old muscle to use and maintain dietary amino acids. Recent studies in old rats have shown that muscle protein synthesis is blunted during balanced feeding (10). In humans, muscle protein synthesis has been found to be slower in elderly compared with young controls during a 5-h meal (11). However, when these data were compared with those obtained in different subjects in the fasting state the st...

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Section: Nih-pa Author Manuscriptcontrasting

confidence: 82%

The Response of Muscle Protein Anabolism to Combined Hyperaminoacidemia and Glucose-Induced Hyperinsulinemia Is Impaired in the Elderly

Volpi¹

2000

Journal of Clinical Endocrinology & Metabolism

324

322

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“…This may be due to the decreased rate of protein synthesis that is associated with age, but reports have been inconsistent (3,52,54,55). Previously, we reported that one cellular pathway involved in skeletal muscle protein synthesis (mTOR/p70 S6K1 ) is intact in aged animals, although its magnitude is dramatically reduced (36).…”

Section: Discussionmentioning

confidence: 99%

Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle

Funai¹,

Parkington²,

Carambula³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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. Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 290: R1080 -R1086, 2006. First published November 23, 2005 doi:10.1152/ajpregu.00277.2005In this study, we investigated the effect of age on the association of eukaryotic initiation factor 4E (eIF4E) with eukaryotic initiation factor 4G (eIF4G), as well as the activity of its binding protein (4E-BP1) and the activity of glycogen synthase kinase-3 (GSK-3) after a single bout of rat hindlimb muscle contractile activity elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Tibialis anterior (TA) and plantaris (Pla) muscles from adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 ϫ Brown Norway rats were collected immediately or 6 h after HFES. eIF4E-eIF4G association was elevated at 6 h of recovery in TA (1.9 Ϯ 0.2-fold, P Ͻ 0.05) and immediately and 6 h after exercise in Pla (2.1 Ϯ 0.3-and 2.1 Ϯ 0.7-fold, P Ͻ 0.05) in Y rats. No significant increase was observed in O rats. An increase in 4E-BP1 phosphorylation was observed only 6 h after HFES in TA (5.0 Ϯ 2.0-fold, P Ͻ 0.05) in Y rats. Phosphorylation of GSK-3␣ was increased immediately and 6 h after contraction in TA (1.6 Ϯ 0.3-and 4.1 Ϯ 0.8-fold, P Ͻ 0.05) and Pla (1.7 Ϯ 0.2-and 2.1 Ϯ 0.4-fold, P Ͻ 0.05) in Y rats and remained unaffected in O rats. Phosphorylation of GSK-3␤ was observed only immediately after HFES in TA (1.5 Ϯ 0.2-fold, P Ͻ 0.05) in Y rats. Overall, eIF4E-eIF4G association and phosphorylation of 4E-BP1 and GSK-3 are increased after HFES in adult, but not in aged, animals. These observations suggest that the anabolic response to muscle stimulation is attenuated with aging and may contribute to the limited capacity of hypertrophy in aged animals. sarcopenia; exercise; signaling; hypertrophy AGING IS ASSOCIATED WITH SKELETAL muscle atrophy (sarcopenia), characterized by decreased strength, functional limitations, and physical disability (4,5,15). Although resistance training can increase muscle size and strength, the myogenic response to exercise and the capacity for muscle hypertrophy in older animals and humans appear to be limited (7, 53). The cellular mechanisms responsible for the age-associated decline in response to exercise are not well understood.The mammalian target of rapamycin (mTOR) signaling kinase, which can be activated by Akt/protein kinase B, has emerged as a crucial regulator of skeletal muscle hypertrophy (8, 41). Acute and chronic effects of contractile activity have been described to increase the phosphorylation of mTOR and its downstream target, the 70-kDa ribosomal protein p70 S6K1 (8,10,37,40). p70 S6K1 is pivotal in the control of translation, inasmuch as it regulates a subset of mRNAs containing 5Ј-terminal polypyrimidine tracts (TOP sequences), which encode ribosomal proteins and factors essential to the translational machinery (49). mTOR also phosphorylates eukaryotic initiation factor (eIF) 4E (eIF4E) binding protein (4E-BP1) (16...

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“…Such an imbalance between breakdown and synthesis is smaller in size than that observed in wasting conditions, such as infections or traumatic injuries; however, when protracted over time it can lead to gradual and significant loss of muscle. Since muscle protein degradation has been consistently reported to remain essentially unchanged with advancing age [12][13][14][15][16], there has been an emphasis on studies examining the influence of age on muscle protein synthesis in the basal (postabsorptive) and fed (post-prandial) state. While some researchers have reported a decrease in basal muscle protein synthesis rate with age [17,18], others [14,19] could not confirm those findings in older individuals exhibiting a reduction in muscle mass.…”

Section: Basal Amino Acid and Protein Metabolism In Agingmentioning

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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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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Myofibrillar protein synthesis in young and old human subjects after three months of resistance training

Cited by 103 publications

References 18 publications

The Response of Muscle Protein Anabolism to Combined Hyperaminoacidemia and Glucose-Induced Hyperinsulinemia Is Impaired in the Elderly

The Response of Muscle Protein Anabolism to Combined Hyperaminoacidemia and Glucose-Induced Hyperinsulinemia Is Impaired in the Elderly

Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle

Amino acid metabolism and regulatory effects in aging

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