Issues on Trainability.

Trainability is an adaptive response to given exercise loads and must be localized to the targeted physiological function since exercise-induced acute and chronic adaptations are systemic. Lack of adaptation or moderate level of adaptation in one organ or one physiological function would not mean that other organs or functions would not benefit from exercise training. The most beneficial training load could easily be different for skeletal muscle, brain, the gastro-intestinal track, or the immune systems. Hence, the term of non-responders should be used with caution and just referred to a given organ, cell type, molecular signaling, or function. The present paper aims to highlight some, certainly not all, issues on trainability especially related to muscle and cardiovascular system. The specificity of trainability and the systemic nature of exercise-induced adaptation are discussed, and the paper aims to provide suggestions on how to improve performance when faced with non-responders.

Reactive Oxygen and Nitrogen Species Regulate Key Metabolic, Anabolic, and Catabolic Pathways in Skeletal Muscle.

Reactive oxygen and nitrogen species (RONS) are important cellular regulators of key physiological processes in skeletal muscle. In this review, we explain how RONS regulate muscle contraction and signaling, and why they are important for membrane remodeling, protein turnover, gene expression, and epigenetic adaptation. We discuss how RONS regulate carbohydrate uptake and metabolism of skeletal muscle, and how they indirectly regulate fat metabolism through silent mating type information regulation 2 homolog 3 (SIRT3). RONS are causative/associative signaling molecules, which cause sarcopenia or muscle hypertrophy. Regular exercise influences redox biology, metabolism, and anabolic/catabolic pathways in skeletal muscle in an intensity dependent manner.

Four-week cold acclimation in adult humans shifts uncoupling thermogenesis from skeletal muscles to brown adipose tissue.

KEY POINTS: Muscle-derived thermogenesis during acute cold exposure in humans consists of a combination of cold-induced increases in skeletal muscle proton leak and shivering. Daily cold exposure results in an increase in brown adipose tissue oxidative capacity coupled with a decrease in the cold-induced skeletal muscle proton leak and shivering intensity. Improved coupling between electromyography-determined muscle activity and whole-body heat production following cold acclimation suggests a maintenance of ATPase-dependent thermogenesis and decrease in skeletal muscle ATPase independent thermogenesis. Although daily cold exposure did not change the fibre composition of the vastus lateralis, the fibre composition was a strong predictor of the shivering pattern evoked during acute cold exposure. ABSTRACT: We previously showed that 4 weeks of daily cold exposure in humans can increase brown adipose tissue (BAT) volume by 45% and oxidative metabolism by 182%. Surprisingly, we did not find a reciprocal reduction in shivering intensity when exposed to a mild cold (18°C). The present study aimed to determine whether changes in skeletal muscle oxidative metabolism or shivering activity could account for these unexpected findings. Nine men participated in a 4 week cold acclimation intervention (10°C water circulating in liquid-conditioned suit, 2 h day-1 , 5 days week-1 ). Shivering intensity and pattern were measured continuously during controlled cold exposure (150 min at 4 °C) before and after the acclimation. Muscle biopsies from the m. vastus lateralis were obtained to measure oxygen consumption rate and proton leak of permeabilized muscle fibres. Cold acclimation elicited a modest 21% (P < 0.05) decrease in whole-body and m. vastus lateralis shivering intensity. Furthermore, cold acclimation abolished the acute cold-induced increase in proton leak. Although daily cold exposure did not change the fibre composition of the m. vastus lateralis, fibre composition was a strong predictor of the shivering pattern evoked during acute cold. We conclude that muscle-derived thermogenesis during acute cold exposure in humans is not only limited to shivering, but also includes cold-induced increases in proton leak. The efficiency of muscle oxidative phosphorylation improves with cold acclimation, suggesting that reduced muscle thermogenesis occurs through decreased proton leak, in addition to decreased shivering intensity as BAT capacity and activity increase. These changes occur with no net difference in whole-body thermogenesis.

Effects of Two Different Weight Training Programs on Swimming Performance and Muscle Enzyme Activities and Fiber Type.

The effects of 2 different weight training programs incorporating bench press (BP) and pullover (PO) exercises on swimming performance, power, enzyme activity, and fiber type distribution were studied on 16 men (age = 23 ± 4 years). A 30-second group (n = 6) performed up to 20 repetitions of BP and PO in 30 seconds. The 2-minute group (n = 6) performed a maximum of 80 repetitions of BP and PO in 2 minutes. As participants reached the prescribed 20 or 80 repetitions, the weight was increased 4.5 kg. A third group (n = 4) served as nontraining controls. Exercise groups trained 3 times per week for 6 weeks. Maximal effort swims of 50 and 200 yd were performed before and after training. Training resulted in increases in work on both exercises in both groups pre- to post-training (BP 30 seconds, 722 ± 236-895 ± 250 kg; PO 30 seconds, 586 ± 252-1,090 ± 677 kg; and BP 2 minutes, 1,530 ± 414-1,940 ± 296; PO 2 minutes, 1,212 ± 406-2,348 ± 194, p ≤ 0.05). Swim performances of the 30-second group improved for both the 50-yd (32.0 ± 6.9 seconds, 30.0 ± 5.9 seconds, p ≤ 0.05) and 200-yd swims 200.0 ± 54 seconds, 182 ± 45.1 seconds (p ≤ 0.05), whereas 2-minute training improved only the 200-yd swim (198.3 ± 32.3 seconds, 186.2 ± 32.2 seconds). No changes in swim performance were observed for the control group. Triceps muscle succinate dehydrogenase activities increased (pre 3.48 ± 1.1 µmol · g(-1) wet weight per minute, post 6.25 ± 1.5 µmoles · g(-1) wet weight per minute, p ≤ 0.05) in only the 30-second training group, whereas phosphofructokinase activities and fiber type distribution did not change in either training group. This study has demonstrated that a 30-second 20-repetition weight training program, specific to the swimming musculature without concurrent swim training, improves swimming performances at both 50- and 200-yd distances.

Exercise training increases anabolic and attenuates catabolic and apoptotic processes in aged skeletal muscle of male rats.

Aging results in significant loss of mass and function of the skeletal muscle, which negatively impacts the quality of life. In this study we investigated whether aerobic exercise training has the potential to alter anabolic and catabolic pathways in the skeletal muscle. Five and twenty eight month old rats were used in the study. Aging resulted in decreased levels of follistatin/mTOR/Akt/Erk activation and increased myostatin/Murf1/2, proteasome subunits, and protein ubiquitination levels. In addition, TNF-α, reactive oxygen species (ROS), p53, and Bax levels were increased while Bcl-2 levels were decreased in the skeletal muscle of aged rats. Six weeks of exercise training at 60% of VO2max reversed the age-associated activation of catabolic and apoptotic pathways and increased anabolic signaling. The results suggest that the age-associated loss of muscle mass and cachexia could be due to the orchestrated down-regulation of anabolic and up-regulation of catabolic and pro-apoptotic processes. These metabolic changes can be attenuated by exercise training.

High altitude exposure alters gene expression levels of DNA repair enzymes, and modulates fatty acid metabolism by SIRT4 induction in human skeletal muscle.

We hypothesized that high altitude exposure and physical activity associated with the attack to Mt Everest could alter mRNA levels of DNA repair and metabolic enzymes and cause oxidative stress-related challenges in human skeletal muscle. Therefore, we have tested eight male mountaineers (25-40 years old) before and after five weeks of exposure to high altitude, which included attacks to peaks above 8000m. Data gained from biopsy samples from vastus lateralis revealed increased mRNA levels of both cytosolic and mitochondrial superoxide dismutase. On the other hand 8-oxoguanine DNA glycosylase (OGG1) mRNA levels tended to decrease while Ku70 mRNA levels and SIRT6 decreased with altitude exposure. The levels of SIRT1 and SIRT3 mRNA did not change significantly. However, SIRT4 mRNA level increased significantly, which could indicate decreases in fatty acid metabolism, since SIRT4 is one of the important regulators of this process. Within the limitations of this human study, data suggest that combined effects of high altitude exposure and physical activity climbing to Mt. Everest, could jeopardize the integrity of the particular chromosome.

Redox-regulating sirtuins in aging, caloric restriction, and exercise.

The consequence of decreased nicotinamide adenine dinucleotide (NAD(+)) levels as a result of oxidative challenge is altered activity of sirtuins, which, in turn, brings about a wide range of modifications in mammalian cellular metabolism. Sirtuins, especially SIRT1, deacetylate important transcription factors such as p53, forkhead homeobox type O proteins, nuclear factor κB, or peroxisome proliferator-activated receptor γ coactivator 1α (which controls the transcription of pro- and antioxidant enzymes, by which the cellular redox state is affected). The role of SIRT1 in DNA repair is enigmatic, because it activates Ku70 to cope with double-strand breaks, but deacetylation of apurinic/apyrimidinic endonuclease 1 and probably of 8-oxoguanine-DNA glycosylase 1 decreases the activity of these DNA repair enzymes. The protein-stabilizing effects of the NAD+-dependent lysine deacetylases are readily related to housekeeping and redox regulation. The role of sirtuins in caloric restriction (CR)-related longevity in yeast is currently under debate. However, in mammals, it seems certain that sirtuins are involved in many cellular processes that mediate longevity and disease prevention via the effects of CR through the vascular, neuronal, and muscular systems. Regular physical exercise-mediated health promotion also involves sirtuin-regulated pathways including the antioxidant-, macromolecular damage repair-, energy-, mitochondrial function-, and neuronal plasticity-associated pathways. This review critically evaluates these findings and points out the age-associated role of sirtuins.

Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training.

A decline in mitochondrial biogenesis and mitochondrial protein quality control in skeletal muscle is a common finding in aging, but exercise training has been suggested as a possible cure. In this report, we tested the hypothesis that moderate-intensity exercise training could prevent the age-associated deterioration in mitochondrial biogenesis in the gastrocnemius muscle of Wistar rats. Exercise training, consisting of treadmill running at 60% of the initial Vo(2max), reversed or attenuated significant age-associated (detrimental) declines in mitochondrial mass (succinate dehydrogenase, citrate synthase, cytochrome-c oxidase-4, mtDNA), SIRT1 activity, AMPK, pAMPK, and peroxisome proliferator-activated receptor gamma coactivator 1-α, UCP3, and the Lon protease. Exercise training also decreased the gap between young and old animals in other measured parameters, including nuclear respiratory factor 1, mitochondrial transcription factor A, fission-1, mitofusin-1, and polynucleotide phosphorylase levels. We conclude that exercise training can help minimize detrimental skeletal muscle aging deficits by improving mitochondrial protein quality control and biogenesis.

Nitric oxide: is it the cause of muscle soreness?

Skeletal muscle hosts all of the isoforms of nitric oxide synthase (NOS). It is well documented that nitric oxide (NO) regulates force generation and satellite cell activation, and therefore, damage repair of skeletal muscle. NO can also activate nociceptors of C-fibers, thereby causing the sensation of pain. Although delayed-onset of muscle soreness (DOMS) is associated with decreased maximal force generation, pain sensation and sarcomere damage, there is a paucity of research linking NO and DOMS. The present mini-review attempts to elucidate the possible relationship between NO and DOMS, based upon current literature.

The effect of regular exercise on development of sarcoma tumor and oxidative damage in mice liver.

Regular exercise has the capability of decreasing the incidence and progress of certain cancers. Murine sarcoma, (S-180) cells were transplanted to control (TC), exercise trained (10 week, 1 hour day, 5 times/ week) mice, which had the swimming training terminated at the time of transplantation (ETT), and also to a group of mice that continued to exercise during tumor bearing (ETC). Continuous exercise decreased the size of tumor by about 50%. The accumulation of reactive carbonyl groups (RCD), were not significantly different for any group. The oxidative modification of proteins in the liver of the animals decreased in the exercise- trained non-tumor bearing group compared with control or tumor-bearing groups. No significant alteration was detected in the level of mutant p53. The data indicate that regular exercise retards the development of sarcoma solid tumors and it seems unlikely that massive uncompensated oxidative stress takes place in the tumor. Key pointsRegular exercise has a capability to reduce the inci-dence and progress of certain cancers.Free radicals could act as a promoters and suppres-sors of cancers.Exercise can suppress the development of Sarcoma, but the underlying mechanisms are not known.

Exercise, oxidative stress and hormesis.

Physical inactivity leads to increased incidence of a variety of diseases and it can be regarded as one of the end points of the exercise-associated hormesis curve. On the other hand, regular exercise, with moderate intensity and duration, has a wide range of beneficial effects on the body including the fact that it improves cardio-vascular function, partly by a nitric oxide-mediated adaptation, and may reduce the incidence of Alzheimer's disease by enhanced concentration of neurotrophins and by the modulation of redox homeostasis. Mechanical damage-mediated adaptation results in increased muscle mass and increased resistance to stressors. Physical inactivity or strenuous exercise bouts increase the risk of infection, while moderate exercise up-regulates the immune system. Single bouts of exercise increases, and regular exercise decreases the oxidative challenge to the body, whereas excessive exercise and overtraining lead to damaging oxidative stress and thus are an indication of the other end point of the hormetic response. Based upon the genetic setup, regular moderate physical exercise/activity provides systemic beneficial effects, including improved physiological function, decreased incidence of disease and a higher quality of life.

Effects of exercise on brain function: role of free radicals.

Reactive oxygen species (ROS) are continuously generated during aerobic metabolism. Certain levels of ROS, which could be dependent on the type of cell, cell age, history of ROS exposure, etc., could facilitate specific cell functions. Indeed, ROS stimulate a number of stress responses and activate gene expression for a wide range of proteins. It is well known that increased levels of ROS are involved in the aging process and the pathogenesis of a number of neurodegenerative diseases. Because of the enhanced sensitivity of the central nervous system to ROS, it is especially important to maintain the normal redox state in different types of neuro cells. In the last decade it became clear that regular exercise beneficially affects brain function as well, and can play an important preventive and therapeutic role in stroke and in Alzheimer's and Parkinson's diseases. The effects of exercise appear to be very complex and could include neurogenesis via neurotrophic factors, increased capillarization, decreased oxidative damage, and increased proteolytic degradation by proteasome and neprilysin. Data from our and other laboratories indicate that exercise-induced modulation of ROS levels plays a role in the protein content and expression of brain-derived neurotrophic factor, tyrosine recepetor kinase B, and cAMP response element binding protein, resulting in better function and increased neurogenesis. The enhanced activities of proteasome and neprilysin result in decreased accumulation of carbonyls and amyloid beta-proteins, as well as improved memory. It appears that exercise-induced modulation of the redox state is an important means by which exercise benefits brain function, increases the resistance against oxidative stress, and facilitates recovery from oxidative stress.

High altitude and oxidative stress.

Exposure to high altitude, which is associated with decreased oxygen pressure, could result in oxidative/reductive stress, enhanced generation of reactive oxygen and nitrogen species (RONS), and related oxidative damage to lipids, proteins, and DNA. The severity of oxidative challenge is related to the degree of altitude. A wide range of RONS generating systems are activated during exposure to high altitude, including the mitochondrial electron transport chain, xanthine oxidase, and nitric oxide synthase. High altitude appears to weaken the enzymatic and non-enzymatic antioxidant systems, and increased nutritional uptake of antioxidant vitamins are beneficial to reduce the altitude-induced oxidative damage. The pattern of high altitude exposure-associated oxidative damage resembles ischemia/reperfusion injury. The adaptive process to this oxidative challenge requires a relatively long period of time. Physical exercise or an enhanced level of physical activity at high altitude, exacerbates the extent of the oxidative challenge. Therefore, special attention is necessary to curb the degree of oxidative stress.

Community exercise program for older adults recovering from hip fracture: a pilot study.

Community-based rehabilitative exercise programs might be an effective means to improve functional outcomes for hip-fracture patients. The purpose of this study was to evaluate the effectiveness of a community exercise program (CEP) for older adults recovering from hip fracture. Twenty-five older adults (mean age 80.0 +/- 6.0 years; 24 women; 71 +/- 23 days post-hip fracture) participated in this pilot study (17 exercise, 8 control). The CEP involved functional stepping and lower extremity-strengthening exercises. Control participants received only standard outpatient therapy. Measures of functional mobility, balance confidence, falls efficacy, lower extremity strength, and daily physical activity were evaluated at baseline and at 16 weeks. Improvements for self-reported physical activity, mobility, balance, and knee-extensor strength were observed for the CEP group. This study demonstrated that a CEP is beneficial for community-dwelling older adults post-hip fracture.

Attenuation of the development of murine solid leukemia tumor by physical exercise.

The active involvement of physical exercise in the evolution of a variety of cancers is well documented. However, its role in solid leukemia tumor development is essentially unknown. Solid leukemia tumor cells were transplanted into 21 hybrid BDF1 control mice, exercise-trained mice that did not exercise during leukemia and exercise-trained mice that exercised during leukemia. The tumor size of the continuously exercising group was ~50% of that of control and exercise-terminated animals 18 days after the transplantation. The activity of antioxidant enzymes and the levels of lipid peroxidation and 8-hydroxy-2'-deoxyguanosine were not different in the tumors of the three groups. The level of carbonylated proteins was smaller in tumors of continuously exercising animals. The mutant form of cell regulatory protein p53 and vascular endothelial growth factor were present in similar amounts in the tumor cells of each group. On the other hand, the protooncogene Ras and I-kappaB proteins were present in higher concentrations in tumors of continuously exercising rats. The present data suggest that exercise during leukemia attenuates the development of tumors in mice. The selective alteration of regulatory proteins might play a role in the beneficial effects of exercise during leukemia.

Capacidad aerobia máxima y actividad deportiva en mexicanos de 13 a 56 años de edad / Maximum oxygen uptake and sport activity in mexicans

El consumo máximo de oxígeno (VO2máx) de miembros de la ciudad de México, que viven a 2240 m de altitud fue medido para obtener valores de referencia relacionados con el VO2máx de desempeño físicodeportivo, y también para evaluar el impacto de dicha medición de la aptitud cardiorrespiratoria y la actividad deportiva sobre el proceso de envejecimiento. Cieto treinta y ocho individuos masculinos, clínicamente sanos y de 13 a 56 años de edad, fueron divididos en grupos de décadas y por su participación deportiva. Las cifras máximas de VO2máx, de potencia (Potmáx) y de frecuencia cardíaca (FCmáx) fueron medidos directamante mediante un sistema de espirometría de circuito abierto, cuando los sujetos hacían ejercicio sobre un ergómetro de bicicleta. El índice de potencia máxima (IPmáx) fue estimado. Del VOmáx se observó que la actividad deportiva afecta positivamente el poder aerobio y "contraresta" la disminución de FCmáx, VO2máx, Potmáx, e IPmáx relacionados con el envejecimiento