Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3&beta;/4E-BP1, and muscle atrophy, including TNF&alpha;/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 &plusmn; 0.2 years) and 16 older (70 &plusmn; 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40&ndash;45% in the type II muscle fibers. TNF&alpha; and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3&beta; were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNF&alpha;, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.<br /

Semiautomatic Training Load Determination in Endurance Athletes

Background: Despite endurance athletes recording their training data electronically, researchers in sports cardiology rely on questionnaires to quantify training load. This is due to the complexity of quantifying large numbers of training files. We aimed to develop a semiautomatic postprocessing tool to quantify training load in clinical studies. Methods: Training data were collected from two prospective athlete’s heart studies (Master Athlete’s Heart study and Prospective Athlete Heart study). Using in-house developed software, maximal heart rate (MaxHR) and training load were calculated from heart rate monitored during cumulative training sessions. The MaxHR in the lab was compared with the MaxHR in the field. Lucia training impulse score, based on individually based exercise intensity zones, and Edwards training impulse, based on MaxHR in the field, were compared. A questionnaire was used to determine the number of training sessions and training hours per week. Results: Forty-three athletes recorded their training sessions using a chest-worn heart rate monitor and were selected for this analysis. MaxHR in the lab was significantly lower compared with MaxHR in the field (183 ± 12 bpm vs. 188 ± 13 bpm, p < .01), but correlated strongly (r = .81, p < .01) with acceptable limits of agreement (±15.4 bpm). An excellent correlation was found between Lucia training impulse score and Edwards training impulse (r = .92, p < .0001). The quantified number of training sessions and training hours did not correlate with the number of training sessions (r = .20) and training hours (r = −.12) reported by questionnaires. Conclusion: Semiautomatic measurement of training load is feasible in a wide age group. Standard exercise questionnaires are insufficiently accurate in comparison to objective training load quantification

Overcoming Target Driven Fratricide for T Cell Therapy

Chimeric Antigen Receptor (CAR) T cells expressing the fusion of the NKG2D protein with CD3ζ (NKG2D-CAR T Cells) acquire a specificity for stress-induced ligands expressed on hematological and solid cancers. However, these stress ligands are also transiently expressed by activated T cells implying that NKG2D-based T cells may undergo self-killing (fratricide) during cell manufacturing or during the freeze thaw cycle prior to infusion in patients. To avoid target-driven fratricide and enable the production of NKG2D-CAR T cells for clinical application, two distinct approaches were investigated. The first focused upon the inclusion of a Phosphoinositol-3-Kinase inhibitor (LY294002) into the production process. A second strategy involved the inclusion of antibody blockade of NKG2D itself. Both processes impacted T cell fratricide, albeit at different levels with the antibody process being the most effective in terms of cell yield. While both approaches generated comparable NKG2D-CAR T cells, there were subtle differences, for example in differentiation status, that were fine-tuned through the phasing of the inhibitor and antibody during culture in order to generate a highly potent NKG2D-CAR T cell product. By means of targeted inhibition of NKG2D expression or generic inhibition of enzyme function, target-driven CAR T fratricide can be overcome. These strategies have been incorporated into on-going clinical trials to enable a highly efficient and reproducible manufacturing process for NKG2D-CAR T cells

A New Method for Non-Invasive Estimation of Human Muscle Fiber Type Composition

Background: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT) or type-II fibers and slow-twitch (ST) or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative.status: publishe

Ketone bodies: beyond their role as a potential energy substrate in exercise

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Does ketone ester supplementation really blunt overreaching symptoms during endurance training overload? Reply

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Effects of a novel prototype noncircular chainring on mechanical efficiency in well trained cyclists and triathletes

Introduction: Cycling performance can generally be improved in two different ways: physiological and biomechanical. The gross of research has been done about maximal oxygen uptake (VO2max) and fractional utilization of VO2max on the lactate or ventilatory thresholds. All of these physiological parameters have been shown to have positive relationships with cycling performance (1). On the other hand, more and more studies have recently been developed on biomechanical factors, such as aerodynamics (2) and mechanical efficiency. Therefore researchers have created many shapes and sizes of noncircular chainrings to ameliorate the efficiency of cycling (3). Results from investigations on this topic are rather inconclusive. This text handles about a completely new shape of chainring developed by the company somovedi SAM (Monaco). The hypothesis states that mechanical efficiency will be higher when cycling with the noncircular chainring compared with cycling with a conventional round chainring. Methods: Protocol: 15 well trained cyclists and triathletes participated in this study. They all had at least 2 years of cycling experience, rode there bike for at least 6000km a year and had an average VO2max of 65.5 ml.kg-1.min-1. An incremental maximal exercise test to exhaustion was done as a pre-test before the actual protocol, which consists of two experimental trials on the same day, separated by a 10min seated resting period. Subjects were randomly assigned to start either with the conventional or prototype chaining. They performed the exact same incremental test as mentioned before (pre-test), but had to stop the exercise at 90% of their maximal heart rate. Respiratory gas exchange values and heart rate were measured throughout the whole test. These values were required to calculate mechanical efficiency. Finally, rate of perceived exertion (RPE, Borg) was measured as well. Material: A schematic overview of the chainring is presented in fig 1. The novel chainring has a greater radius at 100° and 260° of the cyclus and a much smaller radius at both top and bottom death center. This would theoretically help the cyclist to generate more power at ±100° of the cyclus and furthermore help him to overcome top and bottom death center. Results: Throughout the test VO2, VCO2, heart rate and Borg were similar for every incremental step (100-220W), no significant differences were found, except for the Borg values at 140 W. We also used values of VO2 and VCO2 to calculate rate of energy expenditure and so mechanical efficiency. Mechanical efficiency tended to be the same for conventional or prototype chainrings at every power output. Conclusions: So overall, no positive effects where found of the noncircular chainring compared with the conventional chainring. Application to competition seems not useful to us. Further research is necessary. References 1. Coyle E.F, Feltner M.E., Kautz S.A., Hamilton M.T., Montain S.J., Baylor A.M., Abraham L.D., Petrek G.W. Physiological and biomechanical factors associated with elite endurance cycling performance. Med Sci Sports Exerc 23:93-107, 1991 2. Jeukendrup A.E., Martin J. Improving cycling performance: how should we spend our time and money. Sports med 31, 559-69, 2001 3. Ericson M.O., Nisell R. Efficiency of pedal forces during ergometer cycling 9, 118-22, 1988status: publishe

ER Stress in Skeletal Muscle : Origin and Metabolic Consequences.

In secretory organs such as the liver, the pancreas and the adipose tissue, endoplasmic reticulum (ER) stress plays a key role in the etiology of cell disturbances implicated in many diseases. Although much less studied, ER stress is also present in skeletal muscle. In the present review, we hypothesize that ER stress may have important metabolic consequences in skeletal muscle