Functional foods for the prevention of disuse muscle atrophy (DMA) are expected to improve the quality of life (QoL) of bedridden people. Ubiquitin ligases targeting muscle protein degradation, atrogin-1 and muscle-specific ring finger protein (MuRF-1), are critical in the degradation of muscle protein, and oxidative stress induced by mitochondrial dysfunction seems to be involved in muscle atrophy. Dietary antioxidants that attenuate the oxidative stress in skeletal muscle are strong candidates as food ingredients for preventing DMA. The antioxidative flavonoid quercetin was found to prevent DMA by attenuating the induction of atrogin-1/MuRF-1 in mice undertaking the tail suspension test. Several studies revealed that dietary quercetin accumulates in skeletal muscle after metabolic conjugation during absorption. There are many arguments that antioxidant activity is essential for dietary flavonoids to exert their preventive effects, but modulation of the IGF-1 signaling pathway is definitively involved in the mechanism of prevention. Nevertheless, dietary flavonoids (including quercetin) may be potential food factors in the prevention of muscle atrophy. Dietary flavonoids are expected to prevent DMA by attenuating oxidative stress derived from mitochondrial dysfunction.

View full abstract

During water exercise, it was established that heart rate, oxygen uptake and body temperature respond to the influence of water pressure, temperature, buoyancy, and viscosity. This review explains the principle and theory that physiological response could become a benefit of health promotion. The heart rate during water immersion is lower than on land. The blood pressure of young subjects in water is much lower than on land at thermo-neutral conditions, while for old subjects it is higher than on land. Blood pressure increases in water with age due to an age-associated reduction in vascular dispensability. Water pressure and vascular elasticity can affect systolic blood pressure. Capillary vessels expand after exercise in water. When the water level is increased, the volume of the venous return seems to increase; and when the water level decreases, the volume of the venous return decreases. The change in volume of venous return depends on exercise intensity. Physiological indexes apparently change with water temperature to even higher and lower levels than the thermo-neutral. Depending on the viscosity of the water, the oxygen consumption changes. Depending on the water level, the load weight changes. Depending on the exercise movement speed, the oxygen consumption changes. The physical characteristics of water could provide an index and a big benefit for health promotion. In addition, one can expect water exercise to have a beneficial preventive effect on lifestyle-related diseases such as obesity and diabetes.

View full abstract

A decrease in skeletal muscle mass and strength, a condition called sarcopenia, occurs with aging. Because sarcopenia is one of the main factors of frailty and the need for nursing care in elderly people, effective treatment measures for it should be established. The skeletal muscle protein synthetic response to food/nutrition is blunted in the elderly and is thought to be the cause of sarcopenia. Therefore, stimulating skeletal muscle protein synthesis is the most effective way to prevent and treat sarcopenia in the elderly. A series of studies demonstrated that the oral intake of essential amino acids is important for promoting skeletal muscle protein synthesis in the elderly, and that the use of an essential amino acid mixture with an increased leucine content of up to 40% (Amino L40) more efficiently stimulated skeletal muscle protein synthesis in the elderly. We confirmed that Japanese women (aged >75 years) with sarcopenia who were prescribed 3 g of Amino L40 twice daily and moderate intensity exercise for 3 months gained muscle mass and strength as well as increased walking speed. Thus, use of the nutritional supplement Amino L40 would be an effective strategy to combat sarcopenia.

View full abstract

Nutrient transporters play significant roles in physiological hormonal and cellular functions as well as in the maintenance of nutrient metabolism. Lifestyle-related disease can be defined as caused by a disturbance in nutrient metabolism as found in diabetes, dyslipidemia, arteriosclerosis, etc. Therefore, deterioration of nutrient transporters by a genetic mutation or abnormal regulation would cause various lifestyle-related diseases. For instance, dysregulation of muscular glucose transport causes hyperglycemia, and impairment of pancreatic glucose transport can be related to inadequate insulin secretion. These deleterious changes in glucose transport can be a cause of diabetes mellitus. Here, we introduce some examples that indicate the relationship between impairment of nutrient transporters and development of lifestyle-related diseases.

View full abstract

Aged individuals with physiological muscle atrophy (sarcopenia) are likely forced into an unloading condition of inactivity such as bed rest and limb-immobilization. Accumulated experimental evidence, obtained with rats, indicates no definite aging effects on the extent of unloading-induced muscle atrophy. However, various suggestions can be deduced from experimental evidence as guidelines for the development of a combined intervention of exercise, nutrition and physical therapies that effectively maintain skeletal muscle as healthy as possible in aged individuals under unloading condition. The deduced guidelines could be summarized as 1) during the unloading period, atrophy and degeneration of especially slow muscle fibers should be attenuated, 2) in the early stage of the reloading period, massive muscle damage should be avoided, and 3) in the recovery period, re-growth of especially slow muscle fibers should be accelerated. This review also emphasizes that experimental evidence is still lacking, indicating the urgent need to stimulate research interest in the combined effects of aging and immobilization so as to improve health longevity in aging societies.

View full abstract

Some β₂-adrenergic agonists (β₂-agonists) can strongly induce muscular hypertrophy, and are prohibited to use as doping drugs for athletes. The pharmacological mechanism for such induced hypertrophy is not clear. These agonists affect many organs via the cAMP-PKA system. Muscular hypertrophy is most likely induced by way of protein synthesis via the IGF-1/PI3K/PKB system and negative myostatin pathway. There are some reports indicating that β₂-agonists might stimulate protein synthesis via the IGF-1/PI3K/PKB system. Furthermore, it inhibits proteolysis via the ATP-dependent ubiquitin-proteasome system (UPS), autophagy-lysosome system and calcium-calpain system. In this review, some discrepancies are introduced between a basic hypertrophic mechanism and inhibited atrophic mechanism using β₂-agonists. Surfaces of muscle fiber might have some various receptors, and the β₂-adrenoceptor might be activated directly by PI3K via Gα_s to trigger skeletal muscle hypertrophy. β₂-agonists might be stimulated to synthesize follistatin of the myostatin inhibitor, as well as to produce satellite cells. Furthermore, increased myostatin may work to determine the size of each muscle fiber, and an increased number of quiescent satellite cells serve as myonuclei donors for hypertrophied muscle fibers. Recently, it was reported that follistatin synthesis was regulated by microRNAs. The effect of microRNA on β₂-agonists is not clear. In the cAMP/PKA/CREB pathway, β₂-agonists might inhibit various proteolytic systems, resulting in an increase of structural proteins. But β₂-agonists have more pharmacological functions like lipolytic action and stimulation of the central nervous system; thus, more research and analysis is needed.

View full abstract

Hyperthermia has been demonstrated as an important factor limiting endurance performance in a hot environment in both human and animal studies. While temperature can affect individual peripheral physiological systems such as muscle contraction characteristics directly, a dominant role for central mechanisms for exercise impairment has been proposed over the past two decades. Exercise-induced hyperthermia may have a direct effect on the central nervous system such as brain temperature, cerebral blood flow, brain activity, cognitive function, brain neurotransmission and neuromuscular activity. In turn, these changes may affect not only the physiological capacity for exercise, but also the athlete’s perception of heat stress, motivation for exercise or pacing strategy. The purpose of this review is to focus on the central mechanisms underlying human limits to exercise in heat. Specifically, the effects of hyperthermia on brain physiology and function will be summarized, along with the potential impact of these changes on regulating exercise capacity.

View full abstract

Aging is associated with progressive loss of muscle mass and strength, which may lead to a geriatric syndrome known as sarcopenia. Sarcopenia was originally defined as loss of muscle mass, however, recent definitions have incorporated other components such as muscle strength and physical performance. Regardless of definition, low muscle mass is a key factor in sarcopenia. Sarcopenia is substantially prevalent among older adults, and is associated with poor functioning. It also predicts adverse health outcomes such as falls, frailty, disability and mortality. Sarcopenia is a multifactorial syndrome; its etiology is complex, and contributing factors interact with each other. However, there are two major modifiable factors that we should target in order to prevent and treat sarcopenia - physical activity and nutrition. Life-course approach may be important, however, it is not too late to benefit from interventions in later life. Appropriate physical activity including resistance exercise and optimal nutrition including adequate protein intake are important in the primary prevention of the sarcopenia process. In order to improve the physical condition of those currently experiencing a sarcopenic state, effective programs are now being developed, some of which use progressive resistance training in combination with specific nutrient supplementations. Life styles and body composition are quite different in Western and Asian countries. There is an urgent need to establish a consensus on the definition of sarcopenia for those of Asian descent. It would be of great help for health professionals as well as clinicians in this area.

View full abstract

Evaluation of peripheral blood leukocytes has been considered a popular window to the immune system and its response. The numeration of leukocytes has long been a practical clinical marker of acute inflammation. Yet, the numbers and function of circulating leukocytes may also change during and after exercise to an extent comparable to inflammatory responses. A considerable amount of effort to elucidate the underlying mechanism of such changes in circulating leukocytes, however, has revealed quite a different picture showing a major contribution of the neuroendocrine system independent of inflammatory processes. Interestingly, a good correlation of the blood leukocyte profile with athletic performance in endurance runners was reported. It is therefore important to understand and interpret observed changes depending on the context to avoid misinterpretation, especially regarding potential immunological risks unlikely to happen from exercise. A review of the literature, therefore, suggests a minor or negligible immune perturbation of exercise.

View full abstract

Skeletal muscle atrophy can result from prolonged periods of skeletal muscle inactivity due to bed rest, denervation, or unloading. Such unloading-associated atrophy of skeletal muscle is characterized by both an increase in protein degradation and a decrease in protein synthesis. Successful treatments for skeletal muscle atrophy could either block protein degradation pathways activated during atrophy, or stimulate protein synthesis pathways induced during skeletal muscle hypertrophy. In this review, we mainly focus on the Insulin-like growth factor 1 (IGF-1)/Insulin receptor substrate 1 (IRS-1) pathway in muscle, because there is increasing evidence indicating that inhibition of this pathway in muscle is involved in the progression of disuse atrophy. We also focus on the signaling pathways that control skeletal muscle atrophy, including muscle atrophy-associated ubiqitin ligases such as Cbl-b, muscle RING finger 1 (MuRF1), and muscle atrophy F-box (MAFbx)/atrogin-1.

View full abstract

Endurance training induces mitochondrial biogenesis and angiogenesis in skeletal muscle. Endurance training also improves insulin sensitivity at both the skeletal muscle and whole body level. Recently, ROS have been suggested to play an important role in endurance training-induced adaptations. However, this hypothesis is not yet fully supported. To advance understanding of the role of ROS and antioxidants in endurance training-induced adaptations, efforts should be made in future studies to clarify the sites of ROS production and the influence of antioxidants on the redox status under each training condition. Effort should also be directed to identifying the signaling pathways involved. In this situation, it should be recognized that in vivo cellular signaling is redundant. Therefore, efforts to evaluate the relative importance and interactions among the multiple cellular signaling pathways involved in each training condition are required. Without elucidating the role of ROS and antioxidants in endurance training-induced adaptations, then evidence-based sound advice regarding antioxidant supplementation cannot be made.

View full abstract

Glutamine is the most abundant free amino acid in the human body. It is important in gluconeogenesis, a precursor for nucleotide synthesis, and the antioxidant function of glutathione (GSH), and is a fuel for immune cells and enterocytes. The plasma concentration of glutamine is decreased in patients with trauma, sepsis and athletes with overtraining. Plasma glutamine increases after short-term exercise and balanced training; however it decreases after prolonged exhaustive exercise and overtraining. When comparing the plasma glutamine in athletes of different types of sports, cyclists have higher concentrations than all other sports. Glutamine intake increases GSH, which is important for scavenging reactive oxygen species (ROS) during exercise. The data presented in this short review indicate that glutamine administration may increase GSH, resulting in upregulated antioxidant activities, and reduce exercise-induced apoptosis of lymphocyte and neutrophil, and muscle damage.

View full abstract

Water exercise is particularly important for lifestyle disease prevention and long-term care prevention, and is prevalent among the middle-aged and elderly population. During water immersion, buoyancy acts on the immersed body and the influence of gravity is reduced. In addition, cardiovascular responses, caused by blood shifts from the abdomen and legs to the thoracic region, occur due to water pressure, unlike in the case of land exercise. Resting water immersion at thermoneutral conditions (about 34°C water temperature) induces an increase in stroke volume, a reduction in heart rate, an increase in cardiac output, and a reduction of total peripheral vascular resistance, unlike resting on land. During water exercise and the recovery phase of water exercise, there are similar cardiovascular responses due to changes in blood flow. The water temperature and water level cause changes in these basic responses. It has been confirmed that water exercise does not lead to excessive responses in blood pressure, and is effective in cardiovascular rehabilitation. In addition, water immersion during the recovery phase after exercise has attracted attention as a rehabilitative exercise modality. Previous studies have suggested that the effects of immersion on cardiovascular response in the rest, exercise, and recovery phases provide benefits to the immersed person, but further studies are needed to confirm the effective application of the methods.

View full abstract

There is considerable indirect proof that a hypobaric-hypoxic environment increases oxidative stress, which is usually reflected by an increase in hepatic TBARS levels and a decrease in Mn-SOD levels. In a hypobaric chamber experiment designed to simulate the summit of Mt. Fuji, we detected an increase in hydroperoxide, an oxidative stress marker, although the percentage increase was lower than that observed at Mt. Fuji. This highlights the compounding effects of environmental factors (ultraviolet rays, temperature differences, etc.) and indicates the importance of conducting measurements in the field. Although the production of oxygen radicals increases with accelerated aerobic metabolism, it has been reported that oxidative stress increases even in hypoxic environments. Activation of xanthine oxidase (XO), that accompanies ischemia-reperfusion (I/R) or an increase in white blood cells, etc. are considered as potential mechanisms by which oxidative stress increases in hypoxic environments. However, these mechanisms have not been fully clarified.

View full abstract

Obesity is associated with the pathogenesis of chronic inflammatory diseases, such as type II diabetes and nonalcoholic steatohepatitis, which in turn have been attributed to the chronic inflammation in visceral adipose tissue and liver. The innate immune system via macrophages, neutrophils and lymphocytes is related to development of chronic inflammation. Exercise has anti-inflammatory effects and may prevent the development of chronic inflammatory diseases. To elucidate mechanisms of chronic inflammation improvement and/or prevention in the local tissue due to exercise is important to ensure development of effective exercise therapy. This review provides information to elucidate the molecular mechanisms from the perspective of immune regulation on the improvement of chronic inflammation due to exercise.

View full abstract

Ankle inversion sprains are the most common football-related injuries. About 74% of patients with residual symptoms such as general ankle instability, the ankle suddenly giving way, or recurrent ankle sprains, may develop chronic ankle instability. Balance training is a common rehabilitation procedure used after an ankle sprain. However, the influence of balance training on the muscle reaction time and muscle chain reaction is still unclear. Accordingly, this study examines how balance training influences muscle reaction time and muscle chain reaction. This controlled laboratory study involved 33 male college football players assessed for existence/non-existence of ankle functional instability (FI). The subjects were then divided into a group of 12 players with FI who underwent balance training (FI group), 12 players without FI who underwent balance training (Con group), and 9 players without FI who did not undergo balance training (NTr group). Muscle reaction times during ankle varus simulation with Trap-door were measured. The main effect was seen between the peroneus muscle group and anterior tibialis muscle in the Con and NTr groups. In the FI group, no significant main effect on the muscle was seen, but the main effect on intervention period was significant. Balance training reduced the muscle reaction time of the FI group. Results suggest that balance training may improve muscle reaction time. However, the absence of a significant difference between the peroneus muscle group and anterior tibialis muscle in the FI group after balance training indicates that the muscle chain reaction did not recover to the level of an uninjured leg.

View full abstract

The objectives of this study were to quantify the contribution of joint motion to dynamic knee valgus and to classify dynamic knee valgus alignment during single-leg jump landing motion in young female basketball players according to the dominant joint motion. Participants were 64 young female basketball players (age 16.1 ± 0.7 years, body mass 58.8 ± 7.8 kg, height 165.4 ± 9.3 cm, and body mass index 21.5 ± 1.8). We collected the motion data with 12 digital video cameras and calculated the knee-in angle and the toe-out angle in the frontal view to select the neutral and dynamic valgus (Knee-in & Toe-out: KI) groups. We also established three-dimensional data of hip, knee, and ankle joint motion. The results demonstrated that the ranges of hip adduction and knee valgus motion were significantly greater in the KI group than in the neutral group (P < 0.0063). In addition, the participants in the KI group were categorized into three different groups: hip dominant type (8 players), knee dominant type (6 players) and foot dominant type (6 players), depending on the dominant relative joint motion for dynamic knee valgus. Our current results suggest that, like other strength training programs, a lower extremity injury prevention program may need to be designed based on detailed kinematic assessment of an individual athlete.

View full abstract

Maturation and aging induce alterations in glucose and protein metabolism, which are responsible for insulin resistance and sarcopenia. In the present study, we examined the effects of long-term (16 weeks) ingestion of diets supplemented with tetrahydrocurcumin (THC) and/or branched-chain amino acids (BCAAs) on glucose tolerance and soleus muscle protein content in mature rats (28 weeks of age). Intraperitoneal glucose tolerance tests (IPGTTs) were performed at week 6 and week 12 during the experimental period. Glucose tolerance was not affected by 6-week supplementation with THC and/or BCAAs, but was improved by supplementation at 12 weeks. A synergistic effect of THC and BCAAs was not observed. The protein content of the soleus muscle was increased by long-term supplementation with BCAAs, but not THC. These results suggest that THC and BCAAs are potentially beneficial supplements to improving maturation (aging)-related metabolic deterioration.

View full abstract