Restriction of food intake (calorie restriction [CR]) in laboratory animals extends their lifespan and delays the onset of various age-associated diseases, including cancer development. Recent studies revealed that the molecular mechanisms underlying CR-mediated anti-aging effects may be regulated by a confined number of signal transduction pathways that are triggered by neuropeptide Y (NPY) neurons in the neuroendocrine system. On the other hand, possible peripheral regulators of the beneficial effects of CR involve a transcriptional regulator complex, the hepatocyte nuclear factor 4α/peroxisome proliferator-activated receptor gamma coactivator 1-α (HNF-4α/PGC-1α) complex. This complex could regulate not only glucose and lipid metabolism, but also DNA damage responses in the liver. Therefore, maintenance of optimal glucose and lipid levels to prevent metabolic syndrome, and activation of the DNA damage response for suppression of tumor development, may depend on the HNF-4α/PGC-1α complex. Hence, small molecules modulating the activity of this complex could be an important target for development of CR mimetics (CRM), which mimic the beneficial effects of CR without actual food restriction.

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Although doping has a long history of use to enhance performance in competition, the sports community has long fought against it, as it destroys the spirit of athletic integrity. Doping is of course currently prohibited, and the World Anti-Doping Agency (WADA) was established in 1999. WADA quickly created the World Anti-Doping Code (WADC) as a universal rule on anti-doping. This code has 5 International Standards by which all sports participants must abide. The Prohibited List International Standard is the definitively accepted list of prohibited substances and methods in sports; and athletes and support personnel should familiarize themselves with the most recent edition. All athletes to whom prohibited substances or methods are administered for legitimate therapeutic use should obtain a Therapeutic Use Exemption (TUE). Doping Control, referring to all processes related to doping tests, is conducted through In-Competition Testing and Out-of-Competition Testing. Japan established its own Japan Anti-Doping Agency (JADA) in 2001. JADA performs approximately 5,000 doping tests annually, and the Japanese incidence of anti-doping rule violations may be significantly less than the global average. The “JADA Car”, produced by JADA, is the world’s first mobile multi-function anti-doping unit. JADA launched its sports pharmacist system in 2010, and has since certified more than 5,000 sports pharmacists. The Japanese national high school curriculum currently involves anti-doping education, and will continue to promote anti-doping activities in Japan.

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Cognitive impairment is a major health and social issue. Over the past decade many studies have reported that engaging in physical activity and exercise training, and a higher level of physical fitness, can postpone the onset of age-associated cognitive decline or reduce its impact. In this review, therefore, we focused on the association between physical fitness, physical activity, exercise training and cognitive function in older adults. It is assumed that physical fitness, including cardiorespiratory fitness, muscle strength, walking ability, balance, reaction time and flexibility are associated with cognitive function. When considering potential determinants of age-associated cognitive decline, active lifestyles are often considered as protective. In recent years, some regular forms of exercise, including resistance training, have been reported as providing potentially useful psychological benefits. More recently, several potential mechanisms that may underlie the association between physical activity or exercise training and reduced risk of cognitive decline have been revealed.

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Despite the variability of internal and external environments, the human central nervous system (CNS) can generate precise and stable perception and motor behaviors. What mechanism enables this ability? Answering this question is one of the significant goals in the human sciences, including neuroscience, cognitive science, physical education and sports science. The Bayesian integration theory proposes that the CNS learns the prior distribution of a task and integrates it with sensory information to minimize the effect of sensory noise. In this article, we introduce psychophysical reports using motor timing and temporal order judgment (TOJ) tasks that support the Bayesian integration theory. Subsequently, we demonstrate the event-related potentials (ERPs) behind Bayesian integration that operates in somatosensory TOJ.

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Sarcopenia is the age-associated loss of skeletal muscle mass and strength that develops slowly over decades and becomes a significant factor to disability among the elderly population. Recent studies have indicated that blunted anabolic response to nutritional stimuli significantly contributes to the development of sarcopenia. In the present article, we will review recent findings on the role of nutritional intake on muscle protein metabolism in the elderly. This review will particularly focus on acute anabolic responses to amino acids and protein intake, age-associated changes in the response of muscle protein to meal intake, and the role of insulin resistance in muscle protein metabolism. The relationship between age-associated decline of sex steroid hormones and muscle anabolism will also be discussed in addition to the benefits of resistance exercise in muscle protein anabolism. Additionally, recent evidence on the time-course of anabolic response, molecular regulation of muscle protein synthesis, and long-term training effects will be discussed. Finally, recent evidence on the cumulative effect of resistance exercise in combination with nutritional supplementation on muscle protein metabolism will be discussed to propose possible preventative measures against sarcopenia.

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During exercise, amino acid oxidation and protein breakdown are enhanced while protein synthesis is suppressed, even though protein does not constitute a quantitatively important energy source. In response to exercise-induced stimulation, various changes in free amino acids occur in skeletal muscle to meet physiological demands. Plasma amino acids are also under the influence of various types of stress, including exercise stress. For example, acute exercise increases alanine and glutamine levels, but decreases glutamate levels in skeletal muscle. At the same time, it increases tryptophan and taurine levels, but decreases glutamine levels in plasma. Prolonged exercise decreases glutamine and glutamate levels, while increasing tyrosine and phenylalanine levels in skeletal muscle. Furthermore, when prolonged exercise-induced changes in amino acid levels are compared between trained and untrained individuals, glutamate and taurine levels in skeletal muscle and phenylalanine, leucine, isoleucine, and tyrosine levels in plasma are higher in trained individuals. This review provides an overview of changes in amino acid levels in skeletal muscle and plasma, with a focus on changes induced by exercise.

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The gaseous signaling molecules, nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H₂S) have been identified as being produced endogenously in a variety of cells, and are also found to be involved in diverse and pivotal pathophysiological roles including neurotransmission, cellular metabolism, immunological/inflammatory responses, and various aspects of cardiovascular regulation in the human body. These gases can diffuse freely through a membrane and exert their own roles when binding with a variety of molecular targets in a cell. These gaseous molecules can also be detected in the exhaled air, and can change their volume in the presence of diseases and/or exercise. However, the real origin and pathophysiological implications of these gases in the exhaled air are largely uncertain. This review attempts to summarize the generation and biological roles of NO, CO and H₂S, and to advert the pathophysiological significance of measuring these gases in exhaled air with respect to exercise and exercise training.

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Exercise causes parallel increases in systemic arterial pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA). This review focused on the potential role of the acute shift in the baroreflex control of RSNA in both increasing and stabilizing AP during exercise, and causing hypotension afterwards. Treadmill exercise shifted the baroreflex curve for RSNA acutely to the right and upward, characterized by a significant increase in the maximum response, about 170%, which could well explain the parallel increases in AP, HR, and RSNA. In contrast, exercise shifted the baroreflex stimulus-response curve for HR upwards in rats, differing from the shift shown for RSNA, suggesting that the dependent variable of baroreflex control has to be specified when shifts in baroreflex stimulus response curves are discussed. During the post-exercise period, the AP-RSNA baroreflex curve was suppressed vertically, with a significant reduction of about 50% shown in the upper plateau without any alteration in the minimum response, which may be the reason for the post exercise hypotension. The loading of cardiopulmonary baroreceptors modulated the baroreflex control of RSNA in a way resembling “Flip-Flop” or “On-Off” type regulation. In part, this may explain the orthostatic intolerance caused by endurance training.

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Regular exercise improves the risk of arterial stiffness by improving arterial endothelial function and regulating smooth muscle tone and proliferation. However, individual responses to exercise training can vary. Gene polymorphism, namely individual differences in the DNA sequence, is a main causal factor of phenotypic variation in adaptations of physiological function and morphology to regular exercise. In the abdominal aorta of aerobically trained rats, more than 300 genes were detected with differential expression. Additionally, many candidate gene polymorphisms, associated with the risk of arterial stiffening, have been identified. Therefore, various vasodilation and vasoconstriction-related gene polymorphisms may be associated with individual variation in the effects of physical exercise and cardiorespiratory fitness on arterial stiffness risks. Recently, several studies reported that gene polymorphisms, such as atrial natriuretic peptide, endothelial nitric oxide synthase, estrogen receptor-α, endothelin receptor-A, endothelin receptor-B, angiotensinogen, angiotensin-converting enzyme, methylenetetrahydrofolate reductase and fatty acid binding protein 2, were associated with individual variation in the effects of physical exercise or cardiorespiratory fitness on arterial stiffness risks. This article reviews the recent findings on genetic factors influencing the effects of exercise on the risk of cardiovascular diseases, i.e., arterial stiffness.

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Natriuretic peptide (NP) release is mainly stimulated by stretching of the myocardium. NP causes diuresis, natriuresis and vasodilation. NP release increases during exercise. Increased NP plays a counter-regulatory role in increased blood pressure during exercise and makes it lower. The source of ANP released during exercise seems to depend on the experimental conditions. Exercise affected guanylate cyclase activity in the kidney and adrenals. Plasma NP concentration is increased in the hypertensive state. Also, exercise increases plasma NP concentration. But when hypertensive model rats swim for more than 30 minutes, plasma ANP concentration decreases to below the resting level.

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Exercise significantly activates the sympathetic nervous system. Sympathetic activation during exercise is governed by both central command and muscle reflex mechanisms (i.e., muscle metabo- and mechano-reflexes), which modulate arterial vascular responses to exercise. Although many studies have reported that exercise causes sympathetic venoconstriction, none have investigated whether both central command and muscle reflex mechanisms also contribute to regulate venous vascular responses to exercise. Therefore, using ultrasound technique, we assessed changes in the cross-sectional area of the superficial vein in the resting limb as an index of venoconstriction during static exercise with and without tendon vibration, and during the post-exercise recovery period with and without muscle ischemia. We found that both central command and the muscle metaboreflex play an important role in regulating the venous vascular system as observed in the arterial vascular system.

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We examined the effects of acute and chronic exercise under hypobaric hypoxia on cardiovascular responses/adaptations to test the hypothesis that cardiovascular adaptations are more effective after exercise under hypobaric hypoxia than under normobaric normoxia. First, we found that a decrease in peripheral resistance and blood pressure (BP) concomitant with an increase in stroke volume (SV) and cardiac output (CO) could be more effectively induced by chronic exercise under hypobaric hypoxia, than under normoxia. Also, the decrease in peripheral resistance and BP might be attributable to a decrease in arterial stiffness and enhanced vasodilatory activity. Second, the effects of acute hypoxic exposure and exercise on arterial stiffness and vasodilatory activity were examined. Arterial stiffness decreased after acute exercise alone, but not after acute hypoxic exposure alone. However, vasodilatory activity was enhanced by hypoxic stimulus, and to greater extent after hypoxic exercise. These findings suggested that stimulation with concomitant exercise and hypoxia could bring about more beneficial vascular responses. Finally, the time course of cardiovascular adaptations to hypobaric hypoxic exercise were accessed, and we found that a significant decrease in BP, accompanied by an increase in SV and CO, occurs within one week of starting the exercise; and that there is a significant decrease in arterial stiffness by the end of the second week. These changes in cardiovascular responses persisted until the end of the training period. Our findings suggest that exercise under hypobaric hypoxia brings about more rapid and effective beneficial cardiovascular adaptations than that under normoxia.

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Mechanical forces induced by skeletal muscle contraction generate intramuscular stresses as well as external tension. Skeletal muscle cells can sense and adapt to mechanical stresses to maintain cellular homeostasis. Compared to the effects of hormone and growth factors (e.g., insulin, insulin-like growth factor, and other cytokines) on physiological and biochemical properties in skeletal muscle, the implications and molecular mechanisms concerning responses of skeletal muscle to mechanical stresses are still largely unclear. In this short review, we focus on the influences of mechanical stresses, especially intramuscular pressure and stretching, on the contraction of skeletal muscles, and review current results from studies examining the effects of mechanical stresses.

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Core body temperature fluctuates within a narrow range due to inherent thermoregulatory control. Anesthetics impair thermostatic mechanisms, which leads to hypothermia during surgical procedures. Hypothermia that arises during surgery is associated with postoperative complications, and it can be prevented by delivering intravenous solutions, containing amino acids, that have a higher thermic effect than other macronutrients. Recent studies using anesthetized rats have determined that infusion of intravenous amino acids increases plasma insulin concentrations under anesthesia much more than while conscious, and stimulates skeletal muscle protein synthesis via the insulin-mTOR pathway. The increases in insulin levels, under anesthesia, contribute to amino acid-induced elevations in skeletal muscle protein synthesis, energy metabolism and core body temperature. Amino acid infusions also elevate protein breakdown in skeletal muscle; and the resultant increase in muscular protein turnover is positively involved in the modification of core body temperature. These collateral results indicate that amino acids play a unique role in the control of core body temperature, which is a vital sign that is closely indicative of changes in physical status.

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Skeletal muscle is the primary site of glucose uptake in humans. Glucose transport activity, which is the rate-limiting step in muscle glucose metabolism, is linearly related to the content of the GLUT-4 isoform of the glucose transporter. Therefore, the level of GLUT-4 in skeletal muscle may be an important determinant of whole-body glucose disposal. It has been well documented that long-term, low- to moderate-intensity endurance exercise training induces an increase in muscle GLUT-4 content. However, emerging evidence suggests that an adaptive increase in GLUT-4 occurs even after a single acute bout of exercise or high-intensity intermittent exercise training. Recent findings also indicate that nutritional status affects GLUT-4 expression in skeletal muscle. This review provides an overview of the effects of exercise and nutritional status on GLUT-4 content in skeletal muscle, and summarizes recent progress in elucidating the molecular regulation of muscle GLUT-4 gene expression by exercise and nutritional stimuli.

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The superior success of East-African endurance runners has stimulated a large amount of interest in exploring valid reasons for their performance, especially for neuromuscular mechanics. This review provides a brief overview of classic neuromuscular interaction during running; and, thereafter, describes a specific neuromuscular interaction alternative to the classic stretch-shortening cycle concept for enhancing the running economy of East-African distance runners.

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We investigated the effects of 4 weeks of running training on the progressive changes in resting blood pressure (BP) and heart rate (HR) that occurred during that period, as well as on the increases in cardiovascular variables and catecholamine levels induced by a novel stress (immobilization stress) in spontaneously hypertensive rats (SHR) and control normotensive Wistar-Kyoto rats (WKY). In addition, rat sensitivity to exogenously infused norepinephrine (NE) was investigated by measuring the induced pressor response. BP was measured by a tail-cuff method (without heating), which is reportedly both sensitive and accurate for noninvasive measurement of BP in conscious rats. Increases in resting systolic BP over the 4-week period were significantly smaller in the trained SHR than in the untrained SHR, but the training had no effect on the changes in resting BP seen in WKY. After the 4-week running training, BP and NE responses to immobilization stress were reduced in the SHR, as was the increase in BP induced by intravenous (IV) infusion of NE. In the WKY, however, neither the BP response to the stress nor that to the IV infusion of NE was changed by running training. These results suggest 1) that such training was beneficial in the SHR, and 2) that the immobilization stress-induced activation of the sympathetic nervous system (as evidenced by the increase in plasma NE) and the sensitivity to NE (as evidenced by the increase in BP induced by exogenous NE) were each attenuated after the 4-week running training in the SHR, with a consequent reduction in the BP response to a novel stress.

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The aim of this study was to examine the effects of oral taurine (2-aminoethanesulfonic acid) administration on the amount of voluntary wheel running as an indicator of recovery from endurance exercise-induced fatigue in ICR mice. We orally administered a single dose of taurine (0.5 mg/g body weight) or physiological saline immediately after treadmill running at 25 m/min for 90 min. After administration, we placed mice in cages with a running wheel and allowed them to run freely in the wheel with free access to food. In the saline-treated group, exercise significantly decreased the amount of voluntary wheel running compared to the non-exercised mice (p < 0.01), while exercise did not decrease the amount of voluntary wheel running in the taurine-treated group. Significant effects of post-exercise taurine administration on voluntary wheel running during 6 h were found (p < 0.05). The 30-min running distance was significantly higher in the taurine-treated group than in the saline-treated group at 1-1.5 h after treadmill exercise (p < 0.05). Blood glucose and liver and skeletal muscle glycogen concentrations after treadmill exercise were similar in both groups at all times. Total food consumption during 6 h of voluntary wheel running showed no difference between the two groups. The ratio of the total running distance to total food consumption was significantly higher in the taurine-treated group than in the saline-treated group (p < 0.05). Our results show that oral taurine administration after endurance exercise increased the amount of voluntary wheel running. Taurine administration may have a positive effect on recovery from endurance exercise-induced fatigue.

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We determined whether, stimulation of mechanosensitive receptors in active muscle (muscle mechanoreflex activation) induces vasoconstriction in the contralateral non-active muscles. In mid-collicular decerebrated rats (n = 9), we measured the blood flow of the left iliac artery when the right Achilles tendon was stretched by 300 g for 30 seconds (s) to stimulate mechanoreceptors in the triceps surae muscles. The stretch significantly increased the mean arterial pressure (MAP: +20 ± 3%, peak increase from baseline; mean ± SEM) and decreased the vascular conductance (VC) in the left iliac artery (–9 ± 1%, averaged over the stimulation period). After cutting the left sciatic nerve, the stretch did not significantly change the VC (+5 ± 1%), while it significantly increased MAP (+13 ± 3%, peak). In conclusion, the muscle mechanoreflex plays a role in mediating vasoconstriction in the contralateral limb via sympathetic activation.

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