Showing papers by "Elena Volpi published in 2013"

Is the Optimal Level of Protein Intake for Older Adults Greater Than the Recommended Dietary Allowance

Abstract: Background. Protein is a macronutrient essential for growth, muscle function, immunity and overall tissue homeostasis. Suboptimal protein intake can significantly impact physical function and overall health in older adults.

Skeletal Muscle Autophagy and Protein Breakdown Following Resistance Exercise are Similar in Younger and Older Adults

Abstract: THE loss of lean muscle mass and strength that occurs with advancing age, sarcopenia, has significant ramifications for the overall health and quality of life of older adults. Exercise is a common intervention used to attenuate the loss of lean mass and strength in older adults; however, research has illustrated an age-related impairment in the protein anabolic response to resistance exercise (RE [1–5]). Specifically, we observed a blunted increase in protein synthesis following an acute bout of RE in older adults compared with younger adults, accompanied with reduced phosphorylation of proteins in the mTOR and MAPK signaling pathways that regulate translation (5). On the other hand, the muscle protein breakdown (MPB) response following RE is less well defined in both younger and older adults and potentially regulated through multiple cellular signaling cascades. An acute bout of eccentric RE in younger men has been shown to increase the fractional breakdown rate (FBR) of skeletal muscle proteins for 24 hours (6). The process most commonly associated with protein degradation following exercise is the ubiquitin proteasome system (UPS [7,8]). Within the UPS are two E3 ubiquitin ligases, MuRF1 (muscle specific RING finger 1) and MAFbx (muscle atrophy F-box, also known as atrogin-1), both regulated through the transcription factor Forkhead box (FoxO3a [9–11]), which is inhibited via phosphorylation by Akt or PKB (12). Protein catabolism following exercise may also be regulated through the autophagy–lysosomal system (13,14). Recent research has identified several key autophagy genes under the control of the Akt–FoxO3a signaling pathway, including light chain 3 (LC3) and GABARAP (10,15–17). Increases in MPB (6) and the expression of atrogenes (7,8) in the UPS pathway have been shown following exercise but less is known regarding the contribution of both the UPS and the autophagasomal–lysosomal system, especially in advancing age. In this study, our aim was to better characterize the MPB response to exercise through two key pathways; the autophagasomal–lysosomal and the UPS in both younger and older adults. We hypothesized that (a) MPB would be primarily regulated through the UPS following RE and (b) aging would alter the skeletal muscle autophagy and MPB response to exercise.

Protein Blend Ingestion Following Resistance Exercise Promotes Human Muscle Protein Synthesis

Abstract: High-quality proteins such as soy, whey, and casein are all capable of promoting muscle protein synthesis postexercise by activating the mammalian target of rapamycin (mTORC1) signaling pathway. We hypothesized that a protein blend of soy and dairy proteins would capitalize on the unique properties of each individual protein and allow for optimal delivery of amino acids to prolong the fractional synthetic rate (FSR) following resistance exercise (RE). In this double-blind, randomized, clinical trial, 19 young adults were studied before and after ingestion of ∼19 g of protein blend (PB) or ∼18 g whey protein (WP) consumed 1 h after high-intensity leg RE. We examined mixed-muscle protein FSR by stable isotopic methods and mTORC1 signaling with western blotting. Muscle biopsies from the vastus lateralis were collected at rest (before RE) and at 3 postexercise time points during an early (0-2 h) and late (2-4 h) postingestion period. WP ingestion resulted in higher and earlier amplitude of blood branched-chain amino acid (BCAA) concentrations. PB ingestion created a lower initial rise in blood BCAA but sustained elevated levels of blood amino acids later into recovery (P < 0.05). Postexercise FSR increased equivalently in both groups during the early period (WP, 0.078 ± 0.009%; PB, 0.088 ± 0.007%); however, FSR remained elevated only in the PB group during the late period (WP, 0.074 ± 0.010%; PB, 0.087 ± 0.003%) (P < 0.05). mTORC1 signaling similarly increased between groups, except for no increase in S6K1 phosphorylation in the WP group at 5 h postexercise (P < 0.05). We conclude that a soy-dairy PB ingested following exercise is capable of prolonging blood aminoacidemia, mTORC1 signaling, and protein synthesis in human skeletal muscle and is an effective postexercise nutritional supplement.

Exercise and nutrition to target protein synthesis impairments in aging skeletal muscle.

Abstract: The loss of skeletal muscle size and function with aging and sarcopenia may be related, in part, to an age-related muscle protein synthesis impairment. In this review, we discuss to what extent aging affects skeletal muscle protein synthesis and how nutrition and exercise can be used strategically to overcome age-related protein synthesis impairments and slow the progression of sarcopenia.

Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults

Abstract: Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to i...

Addition of Carbohydrate or Alanine to an Essential Amino Acid Mixture Does Not Enhance Human Skeletal Muscle Protein Anabolism

Abstract: In humans, essential amino acids (EAAs) stimulate muscle protein synthesis (MPS) with no effect on muscle protein breakdown (MPB). Insulin can stimulate MPS, and carbohydrates (CHOs) and insulin decrease MPB. Net protein balance (NB; indicator of overall anabolism) is greatest when MPS is maximized and MPB is minimized. To determine whether adding CHO or a gluconeogenic amino acid to EAAs would improve NB compared with EAA alone, young men and women (n = 21) ingested 10 g EAA alone, with 30 g sucrose (EAA+CHO), or with 30 g alanine (EAA+ALA). The fractional synthetic rate and phenylalanine kinetics (MPS, MPB, NB) were assessed by stable isotopic methods on muscle biopsies at baseline and 60 and 180 min following nutrient ingestion. Insulin increased 30 min postingestion in all groups and remained elevated in the EAA+CHO and EAA+ALA groups for 60 and 120 min, respectively. The fractional synthetic rate increased from baseline at 60 min in all groups (P < 0.05; EAA = 0.053 ± 0.018 to 0.090 ± 0.039% · h(-1); EAA+ALA = 0.051 ± 0.005 to 0.087 ± 0.015% · h(-1); EAA+CHO = 0.049 ± 0.006 to 0.115 ± 0.024% · h(-1)). MPS and NB peaked at 30 min in the EAA and EAA+CHO groups but at 60 min in the EAA+ALA group and NB was elevated above baseline longer in the EAA+ALA group than in the EAA group (P < 0.05). Although responses were more robust in the EAA+CHO group and prolonged in the EAA+ALA group, AUCs were similar among all groups for fractional synthetic rate, MPS, MPB, and NB. Because the overall muscle protein anabolic response was not improved in either the EAA+ALA or EAA+CHO group compared with EAA, we conclude that protein nutritional interventions to enhance muscle protein anabolism do not require such additional energy.

Endothelial function and the regulation of muscle protein anabolism in older adults

Abstract: Sarcopenia, the loss of skeletal muscle mass and function with aging, is a major contributor to frailty and morbidity in older adults. Recent evidence has emerged suggesting that endothelial dysfunction and insulin resistance of muscle protein metabolism may significantly contribute to the development of sarcopenia. In this article we review: 1) recent studies and theories on the regulation of skeletal muscle protein balance in older adults; 2) the link between insulin resistance of muscle protein synthesis and endothelial dysfunction in aging; 3) mechanisms for impaired endothelial responsiveness in aging; and 4) potential treatments that may restore the endothelial responsiveness and muscle protein anabolic sensitivity in older adults.

Deficiency in repair of the mitochondrial genome sensitizes proliferating myoblasts to oxidative damage.

Abstract: Reactive oxygen species (ROS), generated as a by-product of mitochondrial oxidative phosphorylation, are particularly damaging to the genome of skeletal muscle because of their high oxygen consumption. Proliferating myoblasts play a key role during muscle regeneration by undergoing myogenic differentiation to fuse and restore damaged muscle. This process is severely impaired during aging and in muscular dystrophies. In this study, we investigated the role of oxidatively damaged DNA and its repair in the mitochondrial genome of proliferating skeletal muscle progenitor myoblasts cells and their terminally differentiated product, myotubes. Using the C2C12 cell line as a well-established model for skeletal muscle differentiation, we show that myoblasts are highly sensitive to ROS-mediated DNA damage, particularly in the mitochondrial genome, due to deficiency in 5' end processing at the DNA strand breaks. Ectopic expression of the mitochondrial-specific 5' exonuclease, EXOG, a key DNA base excision/single strand break repair (BER/SSBR) enzyme, in myoblasts but not in myotubes, improves the cell's resistance to oxidative challenge. We linked loss of myoblast viability by activation of apoptosis with deficiency in the repair of the mitochondrial genome. Moreover, the process of myoblast differentiation increases mitochondrial biogenesis and the level of total glutathione. We speculate that our data may provide a mechanistic explanation for depletion of proliferating muscle precursor cells during the development of sarcopenia, and skeletal muscle dystrophies.

Rapamycin does not affect post-absorptive protein metabolism in human skeletal muscle

Abstract: Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis in response to resistance exercise or amino acid ingestion. Objective To determine whether rapamycin administration influences basal post-absorptive protein synthesis or breakdown in human skeletal muscle. Materials/Methods Six young (26 ± 2 years) subjects were studied during two separate trials, in which each trial was divided into two consecutive 2 h basal periods. The trials were identical except during one trial a single oral dose (16 mg) of rapamycin was administered immediately prior to the second basal period. Muscle biopsies were obtained from the vastus lateralis at 0, 2, and 4 h to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I and LC3B-II protein) associated with each 2 h basal period. Results During the Control trial, muscle protein synthesis, whole body protein breakdown (phenylalanine Ra), mTORC1 signaling, and markers of autophagy were similar between both basal periods (p > 0.05). During the Rapamycin trial, these variables were similar to the Control trial (p > 0.05) and were unaltered by rapamycin administration (p > 0.05). Thus, post-absorptive muscle protein metabolism and mTORC1 signaling were not affected by rapamycin administration. Conclusions Short-term rapamycin administration may only impair protein synthesis in human skeletal muscle when combined with a stimulus such as resistance exercise or increased amino acid availability.

Protein Blend Ingestion Following Resistance Exercise Promotes Human Muscle

Abstract: High-quality proteins such as soy, whey, and casein are all capable of promoting muscle protein synthesis postexercise by activating the mammalian target of rapamycin (mTORC1) signaling pathway. We hypothesized that a protein blend of soy and dairy proteins would capitalize on the unique properties of each individual protein and allow for optimal delivery of amino acids to prolong the fractional synthetic rate (FSR) following resistance exercise (RE). In this double-blind, randomized, clinical trial, 19 young adults were studied before and after ingestion of ;19 g of protein blend (PB) or ;18 g whey protein (WP) consumed 1 h after high-intensity leg RE. We examined mixed-muscle protein FSR by stable isotopic methods and mTORC1 signaling with western blotting. Muscle biopsies from the vastus lateralis were collected at rest (before RE) and at 3 postexercise time points during an early (0–2 h) and late (2–4 h) postingestion period. WP ingestion resulted in higher and earlier amplitude of blood BCAA concentrations. PB ingestion created a lower initial rise in blood BCAA but sustained elevated levels of blood amino acids later into recovery (P < 0.05). Postexercise FSR increased equivalently in both groups during the early period (WP, 0.078 6 0.009%; PB, 0.088 6 0.007%); however, FSR remained elevated only in the PB group during the late period (WP, 0.074 6 0.010%; PB, 0.087 6 0.003%) (P < 0.05). mTORC1 signaling similarly increased between groups, except for no increase in S6K1 phosphorylation in the WP group at 5 h postexercise (P < 0.05). We conclude that a soy-dairy PB ingested following exercise is capable of prolonging blood aminoacidemia, mTORC1 signaling, and protein synthesis in human skeletal muscle and is an effective postexercise nutritional supplement. J. Nutr. doi: 10.3945/jn.112.168021.