Field Of Exercise Physiology Research Articles

Extreme Physiology & Medicine: a new journal focussed on integrative human physiology under stress

Extreme Physiology & Medicine: a new journal focussed on integrative human physiology under stress

Circulating Cell-Free DNA

The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer. In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15-20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis or apoptosis of cells in acute exercise settings. Recently, rapid DNA release mechanisms of activated immune-competent cells like NETosis (pathogen-induced cell death including the release of neutrophil extracellular traps [NETs]) have been discovered. cfDNA accumulations might comprise a similar kind of cell death including trap formation or an active release of cfDNA. Just like chronic diseases, chronic high-intensity resistance training protocols induced persistent increases of cfDNA levels. Chronic, strenuous exercise protocols, either long-duration endurance exercise or regular high-intensity workouts, induce chronic inflammation that might lead to a slow, constant release of DNA. This could be due to mechanisms of cell death like apoptosis or necrosis. Yet, it has neither been implicated nor proven sufficiently whether cfDNA can serve as a marker for overtraining. The relevance of cfDNA with regard to overtraining status, performance level, and the degree of physical exhaustion still remains unclear. Longitudinal studies are required that take into account standardized and controlled exercise, serial blood sampling, and large and homogeneous cohorts of different athletic achievement. Furthermore, it is important to establish standardized laboratory procedures for the measurement of genomic cfDNA concentrations by quantitative real-time polymerase chain reaction (PCR). We introduce a new hypothesis based on acute exercise and chronic exposure to stress, and rapid active and passive chronic release of cfDNA fragments into the circulation.

The Morganroth hypothesis revisited: endurance exercise elicits eccentric hypertrophy of the heart

The Morganroth hypothesis revisited: endurance exercise elicits eccentric hypertrophy of the heart

The missing Akt in the mechanical regulation of skeletal muscle mTORC1 signalling and growth

The mammalian target of rapamycin complex 1 (mTORC1) signalling pathway is a primary regulator of skeletal muscle growth. Ten years ago it was reported that the overexpression of Akt in mice resulted in an astonishing amount of skeletal muscle hypertrophy in association with an activation of the mTORC1 signalling pathway (Bodine et al. 2001). However, the identification of the upstream pathways regulating mTORC1 has remained somewhat elusive. Among those of us interested in how mechanical overload induces muscle hypertrophy (e.g. synergistic ablation or muscle contraction performed against a load as is done with resistance exercise training) it seemed logical that insulin-like growth factor 1 (IGF-1) production via an autocrine, paracrine or endocrine mechanism most likely activated mTORC1 in vivo. In fact, since 2001 the majority of studies that have examined muscle mTORC1 signalling in response to loading and/or exercise have typically referred to this as the ‘Akt/mTOR’ signalling pathway. This was the accepted dogma for several years until The Journal of Physiology published a paper by Spangenburg et al. showing that IGF-1 signalling was blocked in mice over-expressing a dominant-negative (non-functional) IGF-1 receptor but that in response to mechanical overload mTORC1 signalling and muscle growth were not altered (Spangenburg et al. 2008). This was the first real challenge to the notion that IGF-1 and activation of PI3K/Akt signalling is a requirement for muscle growth in response to mechanical loading. Subsequently, The Journal also published an ex vivo study showing that mTORC1 activation following mechanical strain was also independent of the Akt signalling pathway (O'Neil et al. 2009). In this issue of The Journal of Physiology Miyazaki and colleagues demonstrate in vivo that early mTORC1 activation and muscle growth following mechanical overload in C57BL/6J mice is also independent of IGF-1/PI3K/Akt signalling (Miyazaki et al. 2011). Using the synergistic ablation model, the authors found that over the course of the next 10 days muscle hypertrophy, total RNA content, and protein turnover (synthesis and breakdown rates) increased. Phosphorylation of S6K1, a key downstream effector of mTORC1, increased within the first day following overload whereas Akt phosphorylation and activity did not increase for another 2–3 days. This finding indicated that the early activation of mTORC1 from mechanical overload was not associated with Akt activity. They confirmed this by using wortmannin (a direct inhibitor of PI3K and insulin-dependent signalling to Akt) and verified that inhibition of Akt signalling did not prevent the early activation of mTORC1. On the other hand, rapamycin administration to the mice did block the overload-induced activation of mTORC1 in vivo. With this newest addition to the muscle biology literature the evidence is clear that mechanical stimulation of mTORC1 and muscle growth can occur independently of IGF-1 and Akt signalling. It has been suggested that MAPK signalling through MEK/ERK is more important for cell cycle regulation than for regulating protein synthesis. However, a second and very novel finding from the Miyazaki study was the demonstration that MEK/ERK signalling resulted in the phosphorylation and inhibition of tuberous sclerosis 2 (TSC2), a negative upstream regulator of mTORC1, which suggests that MEK/ERK signalling may contribute to mTORC1 activation following mechanical overload. This is the first evidence in skeletal muscle indicating that MEK/ERK signalling can regulate mTORC1 activity by phosphorylating TSC2 at the serine 664 site. Interestingly, studies in humans also show an association between ERK1/2 signalling and mTORC1 which implies that activation of both the MAPK and the mTORC1 pathway are essential for maximal stimulation of muscle protein synthesis following resistance exercise (Fry et al. 2011). The two primary findings from Miyazaki and colleagues are that: (1) in vivo skeletal muscle mTORC1 activation and muscle growth during early mechanical overload occurs independently of IGF-1/PI3K/Akt signalling; (2) upstream regulation of mTORC1 during early mechanical overload may also be controlled by the activation of the MEK/ERK signalling pathway. These are original findings that significantly improve our understanding of the cellular mechanisms underlying muscle hypertrophy and highlight the central role of the mTORC1 pathway. In addition, the notion that MAPK activation is also essential for fully stimulating muscle protein synthesis is intriguing and will clearly be a focus of future research. The accumulation of evidence from transgenic mice (Spangenburg et al. 2008; Witkowski et al. 2010), ex vivo studies (O'Neil et al. 2009), the current in vivo study (Miyazaki et al. 2011), and resistance exercise in humans (Drummond et al. 2009) overwhelmingly suggests that mTORC1 activation (independent of IGF-1 or Akt signalling) is required for load-induced muscle growth and protein synthesis. I think the time has now come for us in the muscle biology and exercise physiology field to eliminate the usage of the common phrase or term ‘Akt/mTOR’ in order to better highlight the Akt-independent activation of the mTORC1 signalling pathway when referring to load-induced hypertrophy.

Acknowledging the Immense Contribution of Dr. Roy Shephard in Promoting the Health Benefits of Physical Activity

Dr. Roy Shephard is a world-renowned authority on physical activity and health who has brought tremendous honour and distinction to Canada. Roy is undoubtedly a giant in the field of exercise physiology, not just in Canada, but throughout the world. His accomplishments have had an incredible impact around the world on physical activity and health knowledge and upon public policy relating to physical activity and health. Dr. Shephard is truly one of Canada

Factors defining oxygen uptake at peak exercise in aged people

Maximum oxygen uptake (VO2max) is defined as the highest rates at which oxygen can be taken up and utilized by the body during severe exercise indicating the cardiopulmonary fitness of the individual. It is one of the main variables in the field of exercise physiology and is frequently used to indicate the cardio-respiratory fitness of an individual [1]. Consequently, there has been great interest in identifying the physiological factors that limit VO2max and determining the role of this variable in endurance and anaerobic performances. Today, it is universally accepted that there is a physiological upper limit to the body's ability to consume oxygen. In the scientific literature, an increase in VO2max is the most common method of demonstrating a training effect. In addition, VO2max is frequently used in the development of an exercise prescription in health and disease. Given these applications of VO2max, there has been great interest in identifying the physiological factors that limit VO2max and determining the role of this variable in endurance performance. Aging-related changes occur mainly in the cardiopulmonary and skeletal muscles, bringing about a reduction in physical performance [7]. Such myocardial and peripheral functional changes include a decline in the maximum heart rate, stroke volume, and contractility, and an increase in peripheral vascular resistance. Consequently, the maximal VO2max decreases. The primary aging process, itself genetically associated, occurs both independently of lifestyle and in the absence of disease [4]. Accordingly, one may expect maximal cardiac output to decrease with aging irrespective of lifestyle because of genetic factors. Reduced arteriovenous oxygen difference at maximal effort [6] is the second factor associated with decrease with aging of VO2max. Incremental exercise is characterized by exposing the subjects to a high degree of load which may alter the left ventricular contractility and function [5]. This has the effect of placing a large load on the left ventricular which might have significant effects on oxygen delivery to the working muscles. Thus, oxygen delivery to the working muscle may be reduced, and since metabolic demand during incremental exercise is increased over time to maximum, elderly subjects may maintain the energy supply due to the balance between O2 delivery and extraction. Untrained and trained elderly can increase the response of the central factors i.e., cardiopulmonary without a significant reduction in peripheral ability to extract oxygen at the muscle level. It was found that in elderly subjects, skeletal muscle mitochondrial capacity, tissue blood flow capacity, and oxygen exchange capacity appear to be wellmatched. It seems that intrinsic mitochondrial function and regulation are not altered significantly. Values for cardiac output at peak aerobic exercise are low in the untrained compared to the trained at maximal aerobic exercise. The lower cardiac output in the untrained elderly at peak exercise is related to the limited heart rate reserve, stroke volume, contractility, and to the inappropriate adjustment of the circulation [3, 5]. The augmentation in maximal oxygen uptake in the trained elderly in response to M. Sagiv (*) :D. Ben-Sira : R. Amir Sports Medicine and Rehabilitation Division, Zinman College of Physical Education and Sport Sciences Wingate, Netany, Israel 42902 e-mail: sagiv-moran@wincol.ac.il

Muscling in on microarrays

Adaptations that are the result of exercise require a multitude of changes at the level of gene expression. The mechanisms involved in regulating these changes are many, and can occur at various points in the pathways that affect gene expression. The completion of the human genome sequence, along with the genomes of related species, has provided an enormous amount of information to help dissect and understand these pathways. High-throughput methods, such as DNA microarrays, were the first on the scene to take advantage of this wealth of information. A new generation of microarrays has now taken the next step in revealing the mechanisms controlling gene expression. Analysis of the regulation of gene expression can now be profiled in a high-throughput fashion. However, the application of this technology has yet to be fully realized in the exercise physiology community. This review will highlight some of the latest advances in microarrays and briefly discuss some potential applications to the field of exercise physiology.

David Bruce Dill: A Man of Many Seasons and Environments—Committed to Life, Heat, and Altitude

Section editor’s note: This paper on the professional life of Dr David Bruce Dill is a departure from the typical ‘‘Lessons From History’’ commentary on a classic original scientific article relevant to wilderness medicine. It is hoped that readers will find this short vignette of Dr Dill, a personality who contributed so much to the field of environmental physiology, enjoyable and informative reading. David ‘‘Bruce’’ Dill (1891‐1986) was widely and affectionately known throughout his life as a scientist, colleague, and friend. As a pioneer in the fields of exercise and environmental physiology, physiochemical properties of blood, and aging, he made significant and lasting contributions. The 20 years Dill spent as research director of Harvard’s renowned Fatigue Laboratory was an era of highly productive research in high-altitude, tropical, and desert environments. His pursuit of research and passion for life lead him to many environments, starting in his early years at Harvard and continuing until his 95th year. Born in Kansas, Dill was raised by relatives after the death of his parents and ultimately moved to California. He was graduated from Occidental College in Los Angeles with a bachelors of science degree in chemistry and received a masters of arts degree and a PhD in chemistry from Stanford University. Through his association with his doctoral advisor, Professor C. L. Alsberg, he obtained a National Research Council Fellowship (1925‐1927) at Harvard University with Lawrence J. Henderson. 1 While at Harvard, Dill was introduced to many scientists, establishing many lasting friendships. He worked with A. V. Bock during research on physiochemical properties of blood at the Massachusetts General Hospital, and their professional and personal relationship continued in the following years. In 1927, through the encouragement of A. V. Hill, both Dill and Bock wrote an update of Bainbridge’s monograph, The Physiology of Muscular Exercise . 2 This publication is considered pioneer work that made a lasting contribution to the field of exercise physiology. It was Dill’s association with L. J. Henderson that led

Lactate—The bad boy of metabolism, or simply misunderstood?

Lactate has been studied in great depth, particularly in the field of exercise physiology, yet its role in metabolism remains in many ways an enigma to the physiologists, causes consternation to clinicians and confusion to those in training. The aim of this article is to marry what we know about lactate physiology with its clinical relevance and implications in everyday medical practise. The initial approach to this requires an understanding of basic lactate metabolism from which one can then examine the relevance of high blood lactate (hyperlactataemia); whether this is harmful or beneficial and how it relates to critical illness.

Human skeletal muscle energy metabolism: when a physiological model promotes the search for new technologies.

The idea that muscle function and, in fact, the function of all living tissues may be described by physical laws appeared in the second half of the 19th century. During this period, Helmoltz (Uber die Erhaltung der Kraft, 1847) showed that the principle of energy conservation may be applied to living systems. In the field of exercise physiology, this idea has been subsequently developed by Rodolfo Margaria's (1901-1983) School and the mathematical formalization of the theory has succeeded in the bioenergetic model. During the last 20 years methodical and critical study of the bioenergetic model has been carried out by Paolo Cerretelli, one of the most important heirs of Rodolfo Margaria's School. Original results and technological developments have been generated by his activity and many young scientists have been educated in this approach. The present paper wants to present the modern history of the bioenergetic model and is dedicated to Paolo Cerretelli on the occasion of his seventieth birthday.

Scientific contributions of A. V. Hill: exercise physiology pioneer.

Beginning in 1910, A. V. Hill performed careful experiments on the time course of heat production in isolated frog muscle. His research paralleled that of the German biochemist Otto Meyerhof, who measured the changes in muscle glycogen and lactate during contractions and recovery. For their work in discovering the distinction between aerobic and anaerobic metabolism, Hill and Meyerhof were jointly awarded the 1922 Nobel Prize for Physiology or Medicine. Because of Hill's interest in athletics, he sought to apply the concepts discovered in isolated frog muscle to the exercising human. Hill and his colleagues made measurements of O(2) consumption on themselves and other subjects running around an 85-m grass track. In the process of this work, they defined the terms "maximum O(2) intake," "O(2) requirement," and "steady state of exercise." Other contributions of Hill include his discoveries of heat production in nerve, the series elastic component, and the force-velocity equation in muscle. Around the time of World War II, Hill was a leading figure in the Academic Assistance Council, which helped Jewish scientists fleeing Nazi Germany to relocate in the West. He served as a member of the British Parliament from 1940 to 1945 and as a scientific advisor to India. Hill's vision and enthusiasm attracted many scientists to the field of exercise physiology, and he pointed the way toward many of the physiological adaptations that occur with physical training.

ランニングにおける最適ペース配分に関する研究

Two different bioenergetic power resources, anaerobic power and aerobic power, are supplied to human muscular exercise. In the field of exercise physiology, a great deal of experimental knowledge has been gathered, however, mathematical model of the power supply has not been determined. This paper describes the mathematical model of human bioenergetics and demonstrates some optimal running paces in long distance. On this study, the optimal control problem is to maximize the distance reached by 16.5 minute running. From the result of optimal solution, in the long distance running events, concentrated anaerobic power must be supplied at the last purt. As to compare with real running pace, this mathematical solution can be approximated to the real 5000 meter running event.

A computational method for determination of the individual anaerobic threshold

The individual anaerobic threshold (IAT) has received attention recently in the field of exercise physiology. The IAT is defined as the point during progressive exercise when lactate climination from the blood is both maximal and equal to the diffusion from the working muscles. It has been theorized that an individual can maintain exercise for relatively long periods when working at the IAT. A common method for determination of the IAT is to perform a visual determination from plots of lactate concentration versus power output. This paper briefly describes the theoretical basis for determination of the IAT and presents an algorithm for its accurate calculation.