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L-leucine (LEU) deprivation decreases protein synthesis and increases the rates of protein degradation. Whey protein hydrolysate (WPH) is a commonly used supplement that has been shown to prevent L...

We evaluated the pharmacokinetics, safety, and efficacy of l-arginine alpha-ketoglutarate (AAKG) in trained adult men.Subjects participated in two studies that employed a randomized, double-blind, controlled design. In study 1, 10 healthy men (30-50 y old) fasted for 8 h and then ingested 4 g of time-released or non-timed-released AAKG. Blood samples were taken for 8 h after AAKG ingestion to assess the pharmacokinetic profile of L-arginine. After 1 wk the alternative supplement was ingested. In study 2, which was placebo controlled, 35 resistance-trained adult men (30-50 y old) were randomly assigned to ingest 4 g of AAKG (three times a day, i.e., 12 g daily, n = 20) or placebo (n = 15). Participants performed 4 d of periodized resistance training per week for 8 wk. At 0, 4, and 8 wk of supplementation the following tests were performed: clinical blood markers, one repetition maximum bench press, isokinetic quadriceps muscle endurance, anaerobic power, aerobic capacity, total body water, body composition, and psychometric parameters tests. Data were analyzed by repeated measures analysis of variance.In study 1, significant differences were observed in plasma arginine levels in subjects taking non-timed-release and timed-release AAKG. In study 2, significant differences were observed in the AAKG group (P0.05) for 1RM bench press, Wingate peak power, blood glucose, and plasma arginine. No significant differences were observed between groups in body composition, total body water, isokinetic quadriceps muscle endurance, or aerobic capacity.AAKG supplementation appeared to be safe and well tolerated, and positively influenced 1RM bench press and Wingate peak power performance. AAKG did not influence body composition or aerobic capacity.

The Kangasjarvi Zn-Cu deposit is a highly deformed and metamorphosed Paleoproterozoic volcanogenic massive sulphide (VMS) deposit located in the Vihanti-Pyhasalmi base metal mining district of central Finland. The host sequence to the deposit, referred to as the Inner Volcanic Sequence (IVS), is comprised of a bimodal suite of metavolcanic rocks and a regionally extensive tonalite-trondhjemite gneiss (sub-volcanic intrusions?). A separate and perhaps younger sequence of mafi c volcanic rocks, with irregular intervals of undifferentiated intermediate to felsic schists and metalimestones, referred to as the Outer Volcanic Sequence (OVS), are separated from the IVS sequence by intervals of metagreywacke and U-P-bearing graphitic schists. A stratigraphic scheme for rocks within the IVS is proposed based on outcrop observations, locally preserved volcanic textures, aspects of seafl oor-related hydrothermal alteration and lithogeochemistry. In this scheme, rare andesites form the lowermost volcanic stratigraphy and are overlain by typical island-arc basalts that were erupted in a subaqueous setting. Tonalite-trondhjemite subvolcanic intrusions were locally emplaced within andesites and coeval rhyolites were extruded on the basaltic substrate. The extrusion of rhyolites, including high-silica rhyolites, was coeval with regional-scale, pre-metamorphic seafloor hydrothermal alteration and local sulphide mineralization. Extensively altered rhyolites envelope massive sulphides and are underlain by altered basalts. The latter rocks are now characterized by a variety of low-variance metamorphic mineral assemblages (e.g. orthoamphibole-cordierite rocks) and define a domain of intense pre-metamorphic chlorite ± sericite alteration in the stratigraphic footwall of the deposit. The altered nature of these rocks is attributed to reaction with seawater-related hydrothermal fluids within a zone of upflow at or near the seafloor. The fundamental controls on convective hydrothermal circulation and subsequent alteration and massive sulphide mineralization at Kangasjarvi, and possibly elsewhere in the district, share many characteristics with other well-described, ancient VMS deposits (e.g. massive sulphide deposits in the Flin Flon Belt, Manitoba, Canada). These characteristics include: 1) an association with bimodal volcanism developed in extensional settings; 2) a close spatial association with regionally extensive felsic subvolcanic intrusions; and 3) petrogenesis of ore-associated volcanic rocks (e.g. high-silica rhyolites, felsic subvolcanic intrusions) indicative of substantial heat transfer from the mantle to the upper crust and the development of anomalous thermal corridors. These features translate into geochemically distinctive rock types that, when combined with aspects of stratigraphy and pre-metamorphic alteration, may be used to develop regional exploration strategies in the Vihanti-Pyhasalmi district.

Massive sulfide deposits in the Vihanti-Pyhasalmi district, central Finland, are hosted by a highly deformed and metamorphosed bimodal volcanic sequence. Alteration zones that envelop these deposits are composed of cordierite + orthoamphibole ± garnet-bearing rocks (referred to as COR rocks) belonging to upper amphibolite to granulite facies. Outcrops of mafic and felsic COR rocks (MCOR and FCOR) in the vicinity of the Ruostesuo Zn-Cu deposit define mappable layers with distinctive metamorphic mineral assemblages: orthoamphibole + cordierite ± plagioclase ± quartz (M1COR); garnet + orthoamphibole + cordierite ± plagioclase ± quartz (M2COR); quartz + cordierite + biotite ± orthoamphibole ± cummingtonite ± garnet ± plagioclase (F1COR); and quartz + cordierite + garnet + sillimanite (F2COR). These rocks are interlayered with, or grade into, typical amphibolites (i.e., hornblende + plagioclase) and quartz + plagioclase-bearing rocks that are interpreted as least altered mafic and felsic metavolcanic rocks, respectively. Whole-rock geochemical data for least altered metavolcanic rocks and COR rocks at Ruostesuo define three mafic suites (primitive basalts, basaltic andesites, and ferrobasalts) and two felsic suites (R1 and R2 rhyolites). Using a combination of high field strength element ratios and rare earth element profiles, COR rocks can be assigned to all five volcanic suites. Calculated mass changes for the majority of exposed COR rocks at Ruostesuo are similar to those reported for chlorite + quartz assemblages found within the inner core of alteration pipes located below some sea-floor massive sulfide deposits. Relative to least altered precursors, mafic COR rocks have gained Fe, Mg ± S and lost variable amounts of Si, Ca, Na, K, Rb, Ba, Sr, and Eu, which resulted in an average net mass loss of about 10 percent. The bulk composition of most altered mafic COR rocks (near total loss of Ca, Na, K) reflects the proportion of chlorite to quartz within the premetamorphic alteration assemblages and the composition of the chlorite. Mass-change results for altered mafic rocks indicate that basalts at Ruostesuo were altered by an evolved, Fe-rich hydrothermal fluid at high water/rock ratios. Mass changes for COR rocks of the R2 felsic volcanic suite are similar to those of the mafic rocks (enriched in Fe ± Mg and depleted in Ca, Na, K, Rb, Ba, Sr, and Eu) except for significant additions of Si that resulted in net mass gains of 20 to 30 percent. Felsic COR rocks of the R1 volcanic suite show gains in K, Rb, and Ba that are attributed to the formation of premetamorphic sericite during an alteration stage dominated by hydrothermal seawater. In comparison to least altered metavolcanic rocks, mafic and felsic COR rocks are depleted in 18O, with {Delta}18O values 2 to 5 per mil lower than precursor rocks. Estimated temperatures of alteration were 270° to 350°C. These data indicate that the signature of a high-temperature (~300°C) sea-floor hydrothermal upflow zone is preserved within upper amphibolite to granulite facies rocks at Ruostesuo. The stratigraphic boundary between strongly chloritized mafic volcanic rocks and silicified felsic volcanic rocks marks a transition from net mass losses associated with hydrothermal fluid-dominated alteration to net mass gains associated with seawater-dominated alteration. Silicification at or near the boundary between mafic and felsic volcanic rocks may have been the result of conductive cooling or mixing with seawater from above. In the absence of textural or crosscutting relationships indicative of a younging direction, a stratigraphic model is proposed on the basis of the above geochemical constraints. Altered basalts at Ruostesuo represent the exposed base of a chloritic stockwork zone that passes upsection into altered felsic volcanic rocks that host massive Zn-Cu sulfides. This stratigraphic model has significance for the interpretation of other massive sulfide deposits in the Vihanti-Pyhasalmi district and exploration strategies that couple chemostratigraphy with mass-change results. More significantly, the preservation of premetamorphic oxygen isotope values for strongly metamorphosed and locally migmatitic COR rocks indicate that oxygen isotope mapping is a viable exploration tool in the district and in other mineralized upper amphibolite to granulite facies terranes worldwide.

We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses. Additionally, mitochondria from the brain, muscle and liver tissue of long-term-fed rats were analyzed for mitochondrial quantity (maximal citrate synthase activity), quality (state 3 and 4 respiration) and reactive oxygen species (ROS) assays. Liver antioxidant capacity trended higher in short-term KD- and SC + KS-fed versus SC-fed rats, and short-term KD-fed rats exhibited significantly greater serum ketones compared to SC + KS-fed rats indicating that the diet (not KS supplementation) induced ketonemia. In long term-fed rats: (a) serum ketones were significantly greater in KD- versus SC- and SC + KS-fed rats; (b) liver antioxidant capacity and glutathione peroxidase protein was significantly greater in KD- versus SC-fed rats, respectively, while liver protein carbonyls were lowest in KD-fed rats; and (c) gastrocnemius mitochondrial ROS production was significantly greater in KD-fed rats versus other groups, and this paralleled lower mitochondrial glutathione levels. Additionally, the gastrocnemius pyruvate-malate mitochondrial respiratory control ratio was significantly impaired in long-term KD-fed rats, and gastrocnemius mitochondrial quantity was lowest in these animals. Rotarod performance was greatest in KD-fed rats versus all other groups at 2, 4 and 8 months, although there was a significant age-related decline in performance existed in KD-fed rats which was not evident in the other two groups. In conclusion, short- and long-term KD improves select markers of liver oxidative stress compared to SC feeding, although long-term KD feeding may negatively affect skeletal muscle mitochondrial physiology.

Purpose We sought to compare the effects of external pneumatic compression (EPC) and sham when used concurrently with resistance training on performance-related outcomes and molecular measures related to recovery. Methods Twenty (N = 20) resistance-trained male participants (aged 21.6±2.4 years) were randomized to balanced sham or EPC intervention groups. The protocol consisted of 3 consecutive days of heavy, voluminous back squat exercise followed by EPC/sham treatment (Days2-4) and 3 consecutive days of recovery (Days5-7) with EPC/sham only on Days5-6. On Day1 (PRE), and Days3-7, venipuncture, flexibility and pressure-to-pain threshold (PPT) measures were performed. Vastsus lateralis muscle tissue was biopsied at PRE, 1-h post-EPC/sham treatment on Day2 (POST1) and 24-h post-EPC/sham treatment on Day7 (POST2). Isokinetic peak torque was assessed at PRE and POST2. Results Peak isokinetic strength did not change from PRE to POST2 in either group. The PPT was significantly lower on Days3-6 with sham, indicating greater muscle soreness, though this was largely abolished in the EPC group. A significant decrease in flexibility with sham was observed on Day3 (+16.2±4.6% knee joint angle; P0.01). Vastus lateralis poly-ubiquitinated proteins significantly increased at the POST2 time point relative to PRE with sham (+66.6±24.6%; P

Background Human and cell culture studies have demonstrated that phosphatidic acid (PA) can increase muscle mass and anabolic signaling, respectively. However, no in vivo evidence to date has examined whether PA can increase intramuscular anabolic signaling in vivo. The purpose of this study was to examine – a) if PA feeding acutely increases post-prandial muscle protein synthesis (MPS) and anabolic signaling markers; and b) if PA can enhance the post-prandial anabolic effects of whey protein concentrate (WPC). Methods

To examine age-related differences in intramuscular concentrations of adenosine triphosphate (ATP), free creatine (FCr), phosphocreatine (PCr) and total creatine (TCr) and if these differences were related to muscle performance. Forty-two healthy, non-sedentary, males between 20 and 76 years provided muscle samples to determine [ATP], [FCr], [PCr], and [TCr]. Maximal strength and endurance were assessed and correlated with intramuscular variables. Intramuscular [ATP] decreased by 13.5 % (p = 0.013) in the older cohort (18.0 ± 0.6 mmol/kg dry wt) vs. the young cohort (20.8 ± 0.9 mmol/kg dry wt) and was significantly correlated to age (r = −0.38, p = 0.008). No other differences were observed between age groups for intramuscular [PCr], [FCr], [TCr], or [PCr]:[TCr] (p > 0.05). The older cohort consumed significantly less (p

Background The purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes. Methods After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1). Results MSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p

We examined how gavage-feeding the following dietary proteins (10 human eq. g dissolved in 1 ml of water) acutely affected skeletal muscle insulin signaling and anabolism markers 90- and 180-min po...

Fifty-six men (21.4±0.4 yrs) were randomly assigned to one of four double-blinded treatments: 60 g/d maltodextrin (PLA) or 60 g/d whey protein from either a) 80% whey protein concentrate (WPC80), b) high lactoferrin WPC80 (WPC80+), or c) hydrolyzed WPC80 (WPH). All subjects participated in an 8-week resistance training program. Two-way repeated measures ANCOVAs were used for statistical analyses. No between- or within-group (p>0.05 and p>0.0125, respectively) changes were observed for 12-hour fasted blood lipids, glucose, WBC, CK or other clinical chemistry markers of safety; however, all groups reduced (p

We examined how gavage-feeding the following dietary proteins (10 human eq. g dissolved in 1 ml of water) acutely affected omental (OMAT) and inguinal/subcutaneous (SQ) adipose tissue lipolysis mar...

We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVR(non-run) and HVR(non-run)), as well as in rats after 6 days of voluntary wheel running (LVR(run) and HVR(run)). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that 'cell cycle'-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9-10 LVR(non-run) rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9-10 HVR counterparts. However, voluntary running wheel access in our G9-10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats.

To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs. RNA-seq revealed a 37% increase in the total transcript number in the OMAT of obese pigs. Ingenuity Pathway Analysis showed transcripts in obese OMAT were primarily enriched in the following categories: 1) development, 2) cellular function and maintenance, and 3) connective tissue development and function, while transcripts associated with RNA posttranslational modification, lipid metabolism, and small molecule biochemistry were reduced. DAVID and Gene Ontology analyses showed that many of the classically recognized gene pathways associated with adipose tissue dysfunction in obese adults including hypoxia, inflammation, angiogenesis were not altered in OMAT in our model. The current study indicates that obesity in juvenile Ossabaw swine is characterized by increases in overall OMAT transcript number and provides novel data describing early transcriptomic alterations that occur in response to excess caloric intake in visceral adipose tissue in a pig model of childhood obesity.

The cessation of physical activity in rodents and humans initiates obesogenic mechanisms. The overall purpose of the current study was to determine how the cessation of daily physical activity in rats at 49–56 days of age and at 70–77 days of age via wheel lock (WL) affects adipose tissue characteristics. Male Wistar rats began voluntary running at 28 days old and were either killed at 49–56 days old or at 70–77 days old. Two cohorts of rats always had wheel access (RUN), a second two cohorts of rats had wheel access restricted during the last 7 days (7d-WL), and a third two cohorts of rats did not have access to a voluntary running wheel after the first 6 days of (SED). We observed more robust changes with WL in the 70- to 77-day-old rats. Compared with RUN rats, 7d-WL rats exhibited greater rates of gain in fat mass and percent body fat, increased adipocyte number, higher percentage of small adipocytes, and greater cyclin A1 mRNA in epididymal and perirenal adipose tissue. In contrast, 49- to 56-day-old rats had no change in most of the same characteristics. There was no increase in inflammatory mRNA expression in either cohort with WL. These findings suggest that adipose tissue in 70- to 77-day-old rats is more protected from WL than 49- to 56-day-old rats and responds by expansion via hyperplasia.

The purpose of the present study was to partially phenotype male and female rats from generations 8–10 (G8–G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances ( P < 0.001), spent less time running ( P < 0.001), and ran slower ( P < 0.001) than their G8 male and female HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1α mRNA in the plantaris and soleus muscles of LVR and HVR nonrunners, although G8 LVR rats inherently possessed less NADH-positive superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass tended to be greater in both sexes of G9–G10 LVR nonrunners vs. G9–G10 HVR nonrunners ( P = 0.06), body fat percentage was similar between lines. G9–G10 HVRs had fat mass loss after 6 days of running compared with their prerunning values, while LVR did not lose or gain fat mass during the 6-day voluntary running period. RNA deep sequencing efforts in the nucleus accumbens showed only eight transcripts to be >1.5-fold differentially expressed between lines in HVR and LVR nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to potential differences in dopaminergic signaling between lines. This unique animal model provides further evidence as to how exercise may be mechanistically regulated.

The early 21st century has witnessed a steady push by scientists, industry leaders, and government officials to make medicine more personalized. To date, the concept of personalized medicine has referred largely to the field of pharmacogenomics. In contrast, relatively few data exist regarding the application of preventive strategies such as physical exercise in the context of personalized medicine. Within this review, we highlight the extant literature and propose five strategies for scientists that may propel the exercise and sports science fields toward this global goal. Notably, these approaches are in addition to methods to maintain adherence to training – a well-known factor in determining exercise responsiveness. Briefly, these strategies include (1) evaluating participant responses to training at the individual as well as group level; (2) identifying sources of variability in responsiveness to training; (3) optimizing exercise dosing strategies to maximize benefits while minimizing barriers to participation; (4) evaluating the efficacy of multimodal interventions for relevant population subgroups; and (5) increasing the clinical relevance of study populations and outcomes in exercise trials. We look forward to seeing these strategies considered in trials of preventive health interventions such as exercise. Extensive future research in this area is needed for the vision of exercise as a personalized form of medicine to become a reality.

Cerebral computed tomography (CT) scanning has been suggested to play a role in the management of patients before carotid endarterectomy (CEA). This prospective study analyzes the value of CT scanning before elective CEA and the correlation of CT findings to significant carotid stenosis.This study includes 131 consecutive patients considered for CEA during a 2-year period. All patients underwent carotid duplex ultrasonography, carotid arteriography, and CT scanning.Eighty patients (61%) had transient ischemic attacks or prior strokes, and 51 (39%) had nonhemispheric symptoms or were asymptomatic. The CT scan was abnormal in 36 (27%) patients; however, no brain tumors or abnormalities to affect clinical management were revealed. Ninety-two CEAs were performed on 87 patients. Twenty-nine (32%) in the operative group had abnormal CT scans, but these did not influence operative decisions. On the basis of this rate of 0% of patients with CT findings to change surgical management in 92 cases, a maximum true rate of occurrence of up to 5% could be detected with alpha equals 0.05 by sampling a population of this size. Four patients (4%) had postoperative cerebral vascular accidents, and all of these had normal preoperative scans. Patients with 50% or more carotid stenosis on arteriogram were significantly more likely to have abnormal CT scans than patients with less than 50% stenosis (20% versus 7%, p = 0.0034). As carotid stenosis became more significant, the frequency of abnormal CT scans increased (p0.01). The cost of CT scanning was $66,089.50 in this study.Significant carotid stenosis was associated with a higher frequency of abnormal CT scans; however, routine preoperative CT scanning was unnecessary before elective CEA.

Dipeptidyl‐peptidase IV (DPP‐IV) is an enzyme with numerous roles within the body, mostly related to regulating energy metabolism. DPP‐IV is also a myokine, but the stimulus for its release is poorly understood. We investigated the transcription and release of DPP‐IV from skeletal muscle in a three‐part study using C2C12 myotube cultures, an acute rat exercise and postexercise feeding model, and human feeding or human exercise models. When myotubes were presented with leucine only, hydrolyzed whey protein, or chemicals that cause exercise‐related signaling to occur in cell culture, all caused an increase in the mRNA expression of DPP‐IV (1.63 to 18.56 fold change, P

Purpose The impact of prophylactic supplementation of N-acetyl-cysteine (NAC) and epigallocatechin gallate (EGCG) on intramuscular expression of proteolytic genes after unaccustomed eccentric muscle contractions was investigated. Methods Thirty apparently healthy males (mean ± SD: 20.0 ± 1.8 years, 175 ± 7.1 cm, 76.1 ± 16.9 kg) ingested daily either 1800 mg of NAC or 1800 mg of EGCG (98% total polyphenols, 80% total catechins, and 50% EGCG), or 1000 mg of a glucomannan placebo (PLA) in a double blind, prophylactic fashion for 14 days. Subjects then completed an unaccustomed eccentric exercise bout (100 repetitions at 30° s −1 ) using the dominant knee extensors. Skeletal muscle biopsies were collected from the vastus lateralis at baseline and both 6 and 24 h after exercise. The expression of proteolytic genes [i.e., muscle ring-finger 1 (MuRF1), atrogin-1, α-type 20S subunit C2 (HC2), α-type 20S subunit C3 (HC3), ubiquitin protein ligase 3B (UBE3B), μ-calpain, and m-calpain] was quantified using real-time RT-PCR. Separate 3 × 3 (group × time) repeated measures ANOVAs were used to analyze changes in gene expression over time between groups. Results No significant group × time interactions were detected between groups for the expression of any of the atrogenes or calpains ( p > 0.05). Significant main effects for time identified increases in MuRF1 (6 h: 5.3 ± 10.8 fold; p = 0.046), UBE3B (6 h: 5.3 ± 7.7 fold; p = 0.006; 24 h: 3.3 ± 4.5 fold; p = 0.005), and m-calpain expression (6 h: 2.7 ± 4.4 fold; p = 0.045) in all participants following exercise. Increases approached significance in HC2 (6 h: 1.9 ± 2.4 fold; p = 0.079; 24 h: 1.6 ± 1.9 fold; p = 0.084) and m-calpain expression (24 h: 1.8 ± 2.3 fold; p = 0.084) following exercise. Conclusions Prophylactic supplementation of NAC and EGCG did not impact acute changes in skeletal muscle proteolytic gene expression following eccentric exercise. Eccentric muscle contractions elevated MuRF1 and UBE3B, while m-calpain and HC2 mRNA tended to increase.

According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2–19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6–11 yr old fail to obtain the recommended 60 min/day of physical activity and 92% of adolescents fail to achieve this goal [Troiano et al. Med Sci Sports Exerc. 40, 2008]. Nonetheless, invasive mechanistic studies in children linking diminished physical activity with metabolic maladies are lacking for obvious ethical reasons. The rodent wheel lock (WL) model was adopted by our laboratory and others to study how different organ systems of juvenile rats respond to a cessation of daily physical activity. Our WL model houses rats in cages equipped with voluntary running wheels starting at 28 days of age. After a certain period of voluntary running (3 to 6 wk), the wheels are locked, thus preventing the rats' primary source of physical activity. The studies discussed herein suggest that obesity-associated maladies including skeletal muscle insulin resistance, hypothalamic leptin resistance, fatty acid oxidation impairments in skeletal muscle and adipose tissue, nonalcoholic fatty liver disease, and endothelial dysfunction are initiated in juvenile animals that are restrained from voluntary exercise via WL. The use of the juvenile rodent WL or other inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity.

Glaucoma, one of the leading causes of blindness worldwide,1 is generally regarded to result from damage to the retinal ganglion cell axons as they traverse the lamina cribrosa (LC), a structure within the optic nerve head (ONH).2 Although lowering intraocular pressure (IOP) remains the only proven method for preventing or delaying the onset and progression of glaucomatous vision loss, the role of IOP in the neuropathy remains unclear.3–5 This is, at least in part, due to the wide spectrum of individual sensitivity to IOP, wherein significant numbers of individuals with normal IOP develop glaucoma (e.g., normotensive glaucoma), whereas other individuals with elevated IOP show no signs of the disease (e.g., ocular hypertensive).3,4,6 Diagnosis and treatment would benefit from an improved understanding of the effects of IOP on the ONH, and of the factors determining individual sensitivity to IOP. The deformations of the LC produced by variations in IOP have thus been studied with numerical7–14 and experimental15–20 techniques. Consensus is emerging within the ocular biomechanics literature that the lamina cribrosa does not respond to changes in IOP in isolation, but rather that the ONH and peripapillary sclera behave as a mechanical system (Fig. 1).4,5,7,9,10,12,17,18,20 The primary objective of this work was to study the relationship between the anterior–posterior lamina cribrosa deformation (LCD) and scleral canal expansion (SCE) produced by an IOP increase.21 To the best of our knowledge, although several studies have proposed this relationship,4,5,7,9,10,12,17,18,21,22 no study has explored it methodically. Identifying associations between responses to IOP has been a challenge because these result from a complex nonlinear combination of factors, including two- and three-factor interactions.12,21 Ultimately, however, the ability to determine the mechanical sensitivity to IOP of a particular ONH will benefit from an improved understanding of how the factors combine. Figure 1. Schematic representation of how the deformations of the sclera and lamina may be related. When describing the effects of IOP on the LC, a useful conceptual framework has emerged in the last few years: that of the balance between the direct effects of ... In this article we describe the results of a study wherein we used parameterized eye-specific finite element models of normal monkey eyes to predict the IOP-induced LCD and SCE for 768 models of the ONH, with varying tissue mechanical properties and geometries. We analyzed the model predictions to determine whether there is an association between LCD and SCE and, if so, under which conditions. We also analyzed the predicted LCD and SCE to identify ONH characteristics that lead to peculiarly large LCD and SCE, which indicates increased biomechanical sensitivity to IOP.

Muscle progenitor cell (MPC) activity is exercise responsive. Post resistance-exercise alterations in myogenic messenger RNAs (mRNAs) found by us and others may initiate these events. However, these mRNA data in the absence of microscopic MPC activity data have limited this interpretation. Alternatively, with our acute exercise data as our basis, we propose that these genes may control other hypertrophic processes in postmitotic fibers.

Dopamine signaling in the nucleus accumbens (NAc) has been postulated to influence reward development towards drugs of abuse and exercise. Herein, we used generation 4-5 rats that were selectively bred to voluntary run high (HVR) versus low (LVR) distances in order to examine if dopamine-like 1 (D1) receptor modulation in the NAc differentially affects nightly voluntary wheel running between these lines. A subset of generation 5-6 HVR and LVR rats were also used to study the mRNA expression of key genes related to reward and addiction in the NAc (i.e., DRD1, DRD5, DRD2, Nr4a2, FosB, and BDNF). In a crossover fashion, a D1-like agonist SKF 82958 (2 μg per side) or D1-like full antagonist SCH 23390 (4 μg per side) was bilaterally injected into the NAc of HVR and LVR female Wistar rats prior to their high running nights. Notably, during hours 2-4 (between 2000 and 2300) of the dark cycle there was a significant decrement in running distances in the HVR rats treated with the D1 agonist (p=0.025) and antagonist (p=0.017) whereas the running distances in LVR rats were not affected. Interestingly, HVR and LVR rats possessed similar NAc concentrations of the studied mRNAs. These data suggest that: a) animals predisposed to run high distances on a nightly basis may quickly develop a rewarding response to exercise due to an optimal D1-like receptor signaling pathway in the NAc that can be perturbed by either activation or blocking, b) D1-like agonist or antagonist injections do not increase running distances in rats that are bred to run low nightly distances, and c) running differences between HVR and LVR animals are seemingly not due to the expression of the studied mRNAs. Given the societal prevalence of obesity and extraneous physical inactivity, future studies should be performed in order to further determine the culprit for the low running phenotype observed in LVR animals.

PURPOSE To quantify the lamina cribrosa insertion into the peripapillary sclera and optic nerve pia in normal (N) and early experimental glaucoma (EEG) monkey eyes. METHODS Perfusion-fixed optic nerve heads (ONHs) from 21 animals were digitally reconstructed three dimensionally and delineated. Anterior Laminar Insertion Position (ALIP), Posterior Laminar Insertion Position (PLIP), Laminar Insertion Length (LIL; distance between the anterior and posterior laminar insertions), and Scleral Thickness (at the Anterior Sub-arachnoid space) were calculated for each ONH. Animals were pooled into four groups based on the kill condition (N vs. EEG) and perfusion IOP (10, 30, or 45 mm Hg) of each eye: N10-N10 (n = 6), N30/45-N10 (n = 6), EEG10-N10 (n = 3), and EEG30/45-N10 (n = 6). Glaucomatous EEG versus N eye differences in each group and each animal were required not only to achieve statistical significance (P < 0.05) but also to exceed physiologic intereye differences within the bilaterally normal groups. RESULTS ALIP was significantly posterior (outward) in the EEG compared with N10 eyes of the EEG30/45-N10 group and 5 of 9 individual EEG eyes (difference range, 12-49 μm). PLIP was significantly posterior in the EEG eyes of both EEG groups and in 6 of 9 individual EEG eyes (range, 25-83 μm). LIL ranged from 90 to 190 μm in normal eyes and was significantly increased within the EEG eyes of both EEG groups and in 7 of 9 individual EEG eyes (difference range, 30-47 μm). CONCLUSIONS Posterior migration of the lamina cribrosa is a component of early cupping in monkey EEG.

This study examined how multiple bouts of conventional resistance training affected the mRNA expression of transcripts and a protein associated with satellite cell activity in human skeletal muscle. Ten younger men (means ± SE; age, 21.0 ± 0.5 years; body mass, 82.3 ± 4.2 kg; height, 178.4 ± 2.2 cm; percent body fat, 15.4% ± 2.9%) and 10 older men (age, 66.4 ± 1.6 years; body mass, 94.2 ± 3.7 kg; height, 180.9 ± 2.2 cm; percent body fat, 27.4% ± 1.8%) completed 3 lower-body workouts (Monday, Wednesday, Friday; 9 sets of 10 repetitions at 80% 1 repetition maximum). Vastus lateralis muscle biopsies were collected prior to intervention (T1), 48 h following workout 1 (T2), 48 h following workout 2 (T3), and 24 h following workout 3 (T4). Real-time reverse transcription–polymerase chain reaction was performed to assess genes of interest, and muscle proliferating cell nuclear antigen (PCNA) was assessed using Western blotting. The CYCLIN D1 gene was expressed more highly in the older vs. younger men (p < 0.05), whereas the expression of all other genes and muscle PCNA were similar between age groups. MYOD mRNA expression increased at T2 (p < 0.05) and MHCEMB gene expression modestly increased (p < 0.05) at T4 relative to baseline expression values in the younger men. Baseline elevations in CYCLIN D1 mRNA expression in older persons may indicate that a compensatory expression of this transcript is occurring in an attempt to retain the muscle’s proliferative potential. Increases in MYOD and MHCEMB indicate that 1 week of conventional resistance exercise may i\ncrease myogenic activity, including satellite cell proliferation and differentiation, respectively, in younger men.

Androgen signaling occurs primarily via the androgen receptor. Megalin, a low-density lipoprotein endocytic receptor located in various mammalian tissues, has been recently shown to facilitate sex hormone–binding globulin (SHBG) steroid complexes across cell membranes. The purpose of this investigation is to determine if the megalin gene is expressed in human skeletal muscle and if present to determine how megalin and androgen receptor mRNA expression change in response to sequential exercise bouts with respect to aging. Ten younger (age: 18-25 years) and 10 older (age: 60-75 years) men completed 3 workouts (M, W, F) each consisting of 9 sets of lower-body exercises with 10 repetitions per set at 80% 1 repetition maximum. Vastus lateralis muscle biopsies were extracted at baseline (T1), 48 hours after workout 1 (T2) and 2 (T3), and 24 hours after workout 3 (T4), and blood samples were collected before and 5 minutes after each workout. Muscle was analyzed for megalin and androgen receptor expression using gene-specific primers and SYBR green chemistry, and blood was analyzed for serum testosterone, SHBG, and the free androgen index. Megalin was expressed in both young and old subjects across all time points, although no between- or within-group mean differences were detected at any time point. Androgen receptor was expressed higher in young men at all time points compared to in old men (p < 0.05), and a significant correlation (p < 0.05; r = 0.506) was found between serum testosterone and androgen receptor after workout 1. Based on our data, the gene coding for megalin is expressed inside skeletal muscle, but its role, if any, in steroid cellular transport cannot be determined. This finding could lay the groundwork for more mechanistic investigations to better delineate its functional role and its potential as a therapeutic adjunct for androgen-related disorders in healthy and aged populations.

To retest the hypothesis that monkey ONH connective tissues become hypercompliant in early experimental glaucoma (EEG), by using 3-D histomorphometric reconstructions, and to expand the characterization of EEG connective tissue deformation to nine EEG eyes.Trephinated ONH and peripapillary sclera from both eyes of nine monkeys that were perfusion fixed, with one normal eye at IOP 10 mm Hg and the other EEG eye at 10 (n=3), 30 (n=3), or 45 (n=3) mm Hg were serial sectioned, 3-D reconstructed, 3-D delineated, and quantified with 3-D reconstruction techniques developed in prior studies by the authors. Overall, and for each monkey, intereye differences (EEG eye minus normal eye) for each parameter were calculated and compared by ANOVA. Hypercompliance in the EEG 30 and 45 eyes was assessed by ANOVA, and deformations in all nine EEG eyes were separately compared by region without regard for fixation IOP.Hypercompliant deformation was not significant in the overall ANOVA, but was suggested in a subset of EEG 30/45 eyes. EEG eye deformations included posterior laminar deformation, neural canal expansion, lamina cribrosa thickening, and posterior (outward) bowing of the peripapillary sclera. Maximum posterior laminar deformation and scleral canal expansion co-localized to either the inferior nasal or superior temporal quadrants in the eyes with the least deformation and involved both quadrants in the eyes achieving the greatest deformation.The data suggest that, in monkey EEG, ONH connective tissue hypercompliance may occur only in a subset of eyes and that early ONH connective tissue deformation is maximized in the superior temporal and/or inferior nasal quadrants.

This study examined mRNA expression patterns for atrogin-1 and muscle ring finger-1 (MuRF-1) before and 24 hours after a resistance training bout. Furthermore, basal, 5-minute and 24-hour postexercise serum concentrations of cortisol and insulin like growth factor-1 (IGF-1) and the relationships between these hormones and the genetic expression patterns of atrogin-1 and MuRF-1 were examined. Younger and older men completed a resistance exercise bout consisting of 3 × 10 repetitions at 80% of their predetermined 1 repetition maximum for Smith squat, leg press and leg extension. Muscle biopsies from the vastus lateralis were obtained before and 24 hours after exercise. Basal and postexercise gene expression differences between age groups were analyzed using the Mann-Whitney U test, whereas separate 2 × 3 repeated measures analyses of variance were performed to analyze changes in hormone concentrations. Spearman's correlations were performed to examine relationships between gene expression patterns and hormone concentrations. Serum cortisol was significantly greater in younger men before and 24 hours after exercise (p < 0.05), whereas serum IGF-1 was significantly greater in younger men at all time points (p < 0.001). Exercise significantly increased cortisol 5 minutes after exercise in both groups (p < 0.05), whereas older men experienced significant elevations in IGF-1 24 hours postexercise (p < 0.05). At baseline, MuRF-1 gene expression was significantly greater in older men (p = 0.03), whereas no age-related differences were found for atrogin-1 (p = 0.24). Fold change in atrogin-1 and MuRF-1 24 hours postexercise revealed no significant differences between younger and older men. Differential baseline expression of MuRF-1 may suggest a regulatory attempt by the aging transcriptome to accommodate changes necessary for homeostatic maintenance. An enhanced understanding of molecular and genetic level adaptations can aid researchers in developing optimal therapeutic and exercise interventions to mitigate decrements in force, power, and loss of muscle mass seen in aging and many clinical populations.

Background This study's purpose investigated the impact of different macronutrient distributions and varying caloric intakes along with regular exercise for metabolic and physiological changes related to weight loss. Methods One hundred forty-one sedentary, obese women (38.7 ± 8.0 yrs, 163.3 ± 6.9 cm, 93.2 ± 16.5 kg, 35.0 ± 6.2 kg•m-2, 44.8 ± 4.2% fat) were randomized to either no diet + no exercise control group (CON) a no diet + exercise control (ND), or one of four diet + exercise groups (high-energy diet [HED], very low carbohydrate, high protein diet [VLCHP], low carbohydrate, moderate protein diet [LCMP] and high carbohydrate, low protein [HCLP]) in addition to beginning a 3x•week-1 supervised resistance training program. After 0, 1, 10 and 14 weeks, all participants completed testing sessions which included anthropometric, body composition, energy expenditure, fasting blood samples, aerobic and muscular fitness assessments. Data were analyzed using repeated measures ANOVA with an alpha of 0.05 with LSD post-hoc analysis when appropriate. Results All dieting groups exhibited adequate compliance to their prescribed diet regimen as energy and macronutrient amounts and distributions were close to prescribed amounts. Those groups that followed a diet and exercise program reported significantly greater anthropometric (waist circumference and body mass) and body composition via DXA (fat mass and % fat) changes. Caloric restriction initially reduced energy expenditure, but successfully returned to baseline values after 10 weeks of dieting and exercising. Significant fitness improvements (aerobic capacity and maximal strength) occurred in all exercising groups. No significant changes occurred in lipid panel constituents, but serum insulin and HOMA-IR values decreased in the VLCHP group. Significant reductions in serum leptin occurred in all caloric restriction + exercise groups after 14 weeks, which were unchanged in other non-diet/non-exercise groups. Conclusions Overall and over the entire test period, all diet groups which restricted their caloric intake and exercised experienced similar responses to each other. Regular exercise and modest caloric restriction successfully promoted anthropometric and body composition improvements along with various markers of muscular fitness. Significant increases in relative energy expenditure and reductions in circulating leptin were found in response to all exercise and diet groups. Macronutrient distribution may impact circulating levels of insulin and overall ability to improve strength levels in obese women who follow regular exercise.

Background:This investigation examined the safety and efficacy of a silica-based mineral antioxidant complex (MAC) that has been suggested to influence body water and buffer lactate.Methods:In a double-blind, randomized crossover design, male participants completed testing for 3 conditions: water only (baseline), rice flour (placebo), and MAC supplementation. Participants visited the laboratory on 5 occasions: familiarization, baseline, Testing Day 1, washout, and Testing Day 2. Baseline and Testing Days 1 and 2 consisted of fasting blood, pre- to postexercise body-water assessment and determination of VO2peak on a cycle ergometer. The supplementation protocols were separated by 1 wk and balanced to minimize an order effect.Results:No differences between conditions were found for heart rate, blood pressure, or serum-safety markers (p > .05). Before exercise there were no differences between conditions for total body water (TBW), intracellular water (ICW), or extracellular water (ECW). No significant interactive effects for supplementation and exercise were found for TBW, ICW, or ECW (p > .05). A time effect for TBW (p < .01) and ICW (p < .001) was present. Within-group changes in TBW occurred in the MAC condition, and within-group changes for ICW occurred in the MAC and placebo conditions. Ratings of perceived exertion and blood lactate increased (p < .05) with exercise. No significant effects were found for performance variables.Conclusions:MAC supplementation had no impact on aerobic exercise performance and lactate response. Increases in TBW and ICW occurred after MAC consumption, but these changes appeared to have minimal physiological impact.

The purpose of this review is to examine the literature in an attempt to elucidate a biomechanical basis for glaucomatous cupping. In particular, this work focuses on the role of biomechanics in driving connective tissue remodeling in the progression of laminar morphology from a normal state to that of an excavated glaucomatous state. While there are multiple contributing factors to the pathogenesis of glaucoma, we focus on laminar extracellular matrix (ECM) remodeling in glaucoma and the feedback mechanisms and signals that may guide progressive laminar cupping. We review the literature on the potential mechanisms of glaucomatous changes in the laminar ECM at the anatomic, structural, cellular and subcellular levels in the context of the biomechanical paradigm of glaucomatous onset and progression. Several conclusions can be drawn from this review. First, extensive remodeling of the lamina cribrosa ECM occurs in primary open angle glaucoma. Second, there is surprisingly little evidence to support acute mechanical damage to the lamina as the principal mechanism of cupping. Third, ONH astrocytes and lamina cribrosa cells can sense their mechanical environment and respond to mechanical stimuli by remodeling the ECM. Fourth, there is evidence suggesting that chronic remodeling of the lamina results in a progressive posterior migration of the laminar insertion into the canal wall, which eventually results in the posterior lamina inserting into the pia mater. Finally, modeling studies suggest that laminar remodeling may be a biomechanical feedback mechanism through which cells modify their environment in an attempt to return to a homeostatic mechanical environment. It is plausible that biomechanics-driven connective tissue remodeling is a mechanism in the progression of laminar morphology from a normal state to that of a cupped, excavated glaucomatous state.

Glaucoma is a progressive degenerative disease of the eye that, among its other effects, results in extensive alterations of the connective tissues in and around the optic nerve head (ONH). In the advanced stages of glaucoma, the connective tissues of the lamina cribrosa (LC) become posteriorly displaced and excavated beneath Bruch's membrane opening (clinical “cupping”), and the laminar beam network appears compressed or collapsed.1 This change in laminar connective tissue anatomy represents a long-term remodeling process mediated by astrocytes and LC cells2–4 that can compromise axonal function and may result in blindness. Although there is still debate as to whether this remodeling process is driven by mechanical, vascular, or other factors,5,6 it is generally acknowledged that intraocular pressure (IOP) plays a central role in the disease.7–11 Various experimental animal models based on IOP elevation have been developed in attempts to better understand the tissue changes that underlie glaucoma. Of these, the monkey model of glaucoma is most used in studies of the ONH connective tissue, because the monkey has a highly developed LC that undergoes morphologic changes that are very similar to those in human glaucoma.1 Prior work with this model has shown that connective tissue changes begin very early, only weeks after the induction of sustained elevated IOP. Specifically, these changes include posterior migration of the LC surface, thickening of the LC (possibly through recruitment of the immediate retrolaminar septa into the three-dimensional [3-D] LC structure12), expansion of the scleral canal, and a marked increase in the amount of connective tissue comprising the lamina.12,13 Two of the changes that occur very early in the disease process—thickening of the LC and increase in total LC connective tissue volume—seem at odds with the longer term remodeling configuration associated with end-stage glaucoma and most likely represent a transient phase of disease progression. As such, they may provide important clues regarding the initiating events in this long-term remodeling process that eventually results in vision loss. In recent years we have proposed a biomechanical paradigm for glaucoma that integrates mechanical, vascular, and cellular influences to describe the multiple changes that occur over a lifetime within the optic nerve head (ONH) during health and disease.5,14,15 Within this paradigm, we hypothesize that IOP-related stresses and strains within the load-bearing connective tissues of the ONH play a key role in modulating local blood flow, diffusion processes, and cellular activity, such that a state of mechanical and biological homeostasis is maintained. As such, the mechanical and vascular hypotheses of glaucomatous damage become complementary rather than dichotomous, and the dynamics of the entire system as a mechanobiological entity are highlighted. We have described techniques for characterizing the microarchitecture of the LC12 and how this information can be used to computationally model the mechanical environment within the LC and peripapillary sclera by using finite element modeling.16 In the present study, we applied the same techniques to model the biomechanical response of three pairs of monkey eyes with unilateral early experimental glaucoma (EG) to acute IOP elevation. Because of the aforementioned changes in anatomy and microarchitecture of the ONH connective tissues that occur in EG, it is important to understand the concomitant changes in the IOP-related displacements, stresses, and strains that take place in these remodeled EG eyes compared with those in their contralateral normal controls. However, our modeling techniques require target deformations for each model that are ideally based on experimental data. Although there are numerous studies on IOP-related deformation of the ONH surface, there are no published data on in vivo ONH connective tissue mechanical deformation. Recent experimental data derived by using a postmortem, 3-D histomorphometric technique suggest that the LC of normal eyes can move either posteriorly or anteriorly, depending on eye-specific geometric and material property factors, and that the magnitude of this displacement is small (approximately ±7 μm).17 In EG eyes, however, determination of the LC displacement by such 3-D histomorphometric approaches is problematic because it is unclear how to separate the laminar deformation into its permanent (remodeled) and acute (mechanical) IOP-related components (Burgoyne CF, et al. IOVS 2010;51:ARVO E-Abstract 2137). In light of this uncertainty, in the present study we varied the LC material stiffness of each EG and contralateral normal eye to produce a wide range of target LC displacements, both posterior and anterior, and characterized the concomitant changes in scleral canal expansion, and stress and strain in the LC for IOP increase from 10 to 45 mm Hg.

The purpose of this study was to examine the gender effect of daily consumption of a thermogenic drink (TD) containing caffeine, epigallocatechin gallate, and taurine. In a single-blind, matched-pairs, placebo-controlled study, 60 participants (n=30 men and n=30 women) were matched in a balanced fashion according to age and body mass. Participants completed determination of body composition, resting energy expenditure (REE), and serum levels of glycerol and free fatty acids before and after ingesting either 336 mL of a TD or a noncaloric, noncaffeinated placebo (PLA). Participants were supplemented daily with 336 mL of either the TD or PLA and repeated identical testing procedures on day 28. Area under the curve (AUC) analysis on days 0 and 28 were calculated for all blood variables (e.g., glycerol and free fatty acids) and analyzed with REE, respiratory exchange ratio, dietary records, and body composition with separate repeated-measure analyses of variance. On days 0 and 28, REE AUC (p

The current study examined muscle DNA and protein concentrations ([ ]) and the [RNA] (assumed to represent translational capacity), [RNA]:[DNA] (assumed to represent transcriptional efficiency) and [protein]:[RNA] (assumed to represent translational efficiency) in younger vs. older participants during a resting state. Further, changes in muscle [DNA], translational capacity, and transcriptional efficiency were analyzed 24 hours after an unaccustomed resistance exercise bout. Younger (20.9 +/- 0.5 years, 84.0 +/- 5.2 kg, 26.6 +/- 1.8 kg x m(-2); n = 13) and older men (67.6 +/- 1.3 years, 88.7 +/- 4.8 kg, 28.6 +/- 1.4 kg x m(-2); n = 13) reported to the laboratory and completed an unaccustomed bout of lower-body resistance training (i.e., 3 sets of 10 repetitions at 80% 1 repetition maximum for Smith squat, leg press, and leg extensions). Muscle biopsies from the vastus lateralis were obtained before and 24 hours after exercise. Baseline [RNA], [DNA], [protein], and [RNA]:[DNA] were not different between age groups (p0.05). Baseline [protein]:[RNA] was greater in younger vs. older men (p = 0.045), whereas 24-hour postexercise [RNA]:[DNA] tended to be greater in older men (p = 0.087). These findings suggest that a decrease in the efficiency of translational processes occurs in older human skeletal muscle, whereas global transcriptional processes appear to be unaltered when compared with those in younger men. In lieu of these data, it remains apparent that muscle-protein synthesis is impaired in aging skeletal muscle and effective countermeasures such as resistance exercise and nutritional adequacy must be undertaken by older populations to offset this phenomenon.

Purpose: The purpose of this study was to determine if consuming isoenergetic (25 g) doses of carbohydrate or protein versus a noncaloric placebo before conventional resistance training affected the myogenic expression of cell cycle-regulating genes as well as the muscle [DNA] acutely after exercise. Methods: Ten untrained men (mean ± SD: age = 22 ± 4 yr, body mass = 77.8 ± 8.3 kg, percent body fat = 17.8 ± 4.0) participated in three resistance exercise sessions (three sets of 10 repetitions at 80% one-repetition maximum for the bilateral hack squat, leg press, and leg extension exercises) in a crossover fashion, which were preceded by carbohydrate, protein, or placebo ingestion 30 min before training. Presupplement/preexercise and 2- and 6-h postexercise muscle biopsies were obtained during each session and analyzed for fold changes in CDK4, CYCLIN D1, MGF, MYOD, P21CIP1, and P27KIP1 messenger RNA expression using real-time reverse transcriptase-polymerase chain reaction as well as muscle [DNA] using cuvette-based fluorometric methods. Results: Nonparametric statistics were completed, and no conditions × time interaction effects were revealed. Several exercise-mediated responses were found to occur independent of condition: 1) muscle [DNA] increased at 6 h (+40%, P < 0.05), 2) CDK4 expression increased at 6 h (+86%, P < 0.05), 3) MYOD expression increased at 6 h (+98%, P < 0.05), 4) P27KIP1 expression decreased at 2 h (-35%, P < 0.05) and 6 h (-59%, P < 0.001), and 5) P21CIP1 expression substantially increased 2 and 6 h postexercise (+1.250% and +4.670%, respectively, P < 0.001). Conclusions: The tandem DNA and cell cycle regulator gene expression analyses provide preliminary evidence to suggest that satellite cell activation and proliferation may be occurring at early postexercise time points after a conventional resistance exercise bout, a phenomenon that may seemingly be independent of preexercise macronutrient ingestion