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Selenoprotein P is released from the liver and acts through LRP1 in the muscle to contribute to exercise resistance in mouse and man by inhibiting ROS levels via inhibition of AMPK and PGC-1α. Exercise has numerous health-promoting effects in humans 1 ; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly 2 , 3 , 4 . This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine selenoprotein P (SeP) 5 , 6 , 7 causes exercise resistance through its muscle receptor low-density lipoprotein receptor–related protein 1 (LRP1) 8 . SeP-deficient mice showed a 'super-endurance' phenotype after exercise training, as well as enhanced reactive oxygen species (ROS) production, AMP-activated protein kinase (AMPK) phosphorylation 9 and peroxisome proliferative activated receptor γ coactivator (Ppargc)-1α (also known as PGC-1α; encoded by Ppargc1a ) 10 expression in skeletal muscle. Supplementation with the anti-oxidant N -acetylcysteine (NAC) reduced ROS production and the endurance capacity in SeP-deficient mice. SeP treatment impaired hydrogen-peroxide-induced adaptations through LRP1 in cultured myotubes and suppressed exercise-induced AMPK phosphorylation and Ppargc1a gene expression in mouse skeletal muscle—effects which were blunted in mice with a muscle-specific LRP1 deficiency. Furthermore, we found that increased amounts of circulating SeP predicted the ineffectiveness of training on endurance capacity in humans. Our study suggests that inhibitors of the SeP–LRP1 axis may function as exercise-enhancing drugs to treat diseases associated with a sedentary lifestyle.

The aim of the current study was to perform a systematic review and meta-analysis to evaluate the relationship between step count and changes in blood pressure (BP). Studies involving healthy adults and an intervention in the form of brisk walking with a pedometer were included. Net changes in BP and step count in each trial were calculated and pooled. In addition, the pooled net changes of two categories (trials that achieved walking 10,000 steps a day and those that did not) were compared. A meta-regression analysis was performed to examine the relationship between net changes in BP and step count. Fourteen trials were analyzed. Pooled net changes in BP improved significantly (systolic BP, −3.1 mm Hg; diastolic BP, −1.6 mm Hg). When the trials were categorized depending on whether they achieved walking 10,000 steps a day, the pooled net change in systolic BP and diastolic BP did not differ significantly between both groups of subjects. The meta-regression analyses indicated that net change in systolic BP was significantly associated with an increased step count (e.g., systolic BP is expected to decrease approximately 4 mm Hg if increased step count by 2000 steps a day). However, net change in systolic BP was not associated with the step count in an intervention group following the intervention. At present, there is presumably no evidence that walking 10,000 steps a day lowers the BP to any marked degree. In order to reduce systolic BP by walking with a pedometer, one should be mindful of increasing one’s step count.

Purpose Polyphenolic curcumin is known to have potent anti-inflammatory effects; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after eccentric exercise. Methods Fourteen untrained young men (24 ± 1 years) performed 50 maximal isokinetic (120°/s) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later. They took 150 mg of curcumin (theracurmin) or placebo (starch) orally before and 12 h after each eccentric exercise bout in a randomised, crossover design. Maximal voluntary contraction (MVC) torque of the elbow flexors, range of motion of the elbow joint, upper-arm circumference, muscle soreness, serum creatine kinase (CK) activity, and plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration were measured before, immediately after, and 24, 48, 72 and 96 h after each eccentric exercise. Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA. Results MVC torque decreased smaller and recovered faster (e.g., 4 days post-exercise: −31 ± 13 % vs. −15 ± 15 %), and peak serum CK activity was smaller (peak: 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L) for curcumin than placebo condition ( P  < 0.05). However, no significant differences between conditions were evident for other variables, and no significant changes in IL-6 and TNF-α were evident after exercise. Conclusion It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase.

PurposeSleep duration is known to affect physiological and circadian metabolites and human homeostasis. However, little is known about the relationship between sleep quality and metabolite and cognitive function during exercise. Therefore, the aim of the present study was to investigate the impact of sleep quality on metabolite level and cognitive function in female volleyball athletes.MethodsTwelve female volleyball athletes participated in this study. Sleep efficiency was measured for 1 week using NemuriSCAN (Paramount Bed Co. Ltd., Japan) as an index of sleep quality. The subjects were divided into better (n = 6) and lesser (n = 6) sleep quality groups by the median value of sleep efficiency. Saliva samples were collected using a Salimetric oral swab cotton and salivary metabolites were analysed using capillary electrophoresis and time-of-flight mass spectrometry. The subjects performed Stroop tasks (simple and difficult tasks) at rest and during aerobic exercise in recumbent cycle ergometer at light and heavy intensity.ResultsIncreased sleep efficiency was found in the better sleep quality group, whereas total sleep time was similar. There were differences in urea cycle and Krebs cycle metabolites between the two groups; their levels were correlated with sleep efficiency. The difficult-task response time during heavy exercise was faster in the better sleep quality group.ConclusionWe demonstrated that sleep efficiency was associated with urea cycle and Krebs cycle metabolite levels and response time during heavy exercise in volleyball athletes. These results suggested that sleep quality may affect amino acid and energy metabolism and cognitive function during heavy exercise.

Background Physical inactivity and sedentary behaviour (too much sitting) can contribute to renal dysfunction. However, the potential benefits of behavioural change (e.g. replacing sedentary behaviour with physical activity) on renal function are not well understood. We used isotemporal substitution to model potential impacts of behaviours on renal function by replacing time spent in one behaviour to another. Methods In 174 older Japanese adults (age, 50–83 years; females, 76%), the time spent in sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using an uniaxial accelerometer. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C levels. Results In univariate analyses, eGFR was significantly, albeit weakly, correlated with time spent in sedentary behaviour ( r s  = − 0.229), LPA ( r s  = 0.265), and MVPA ( r s  = 0.353). In the isotemporal substitution models, replacement of 30 min/day of sedentary behaviour with an equivalent LPA time was not significantly associated with eGFR ( β  = 2.26, p  = 0.112); however, replacement with an equivalent time of MVPA was beneficially associated with eGFR ( β  = 5.49, p  < 0.05). Conclusions These cross-sectional findings suggest that sedentary behaviour (detrimentally) and physical activity (beneficially) may affect renal function and that replacing sedentary behaviour with MVPA may benefit renal health in older adults.

Background Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. Methods Forty-five women were randomly assigned to four interventions: \"placebo ingestion\" (n = 11), \"curcumin ingestion\" (n = 11), \"exercise training with placebo ingestion\" (n = 11), or \"exercise training with curcumin ingestion\" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. Results There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. Conclusions These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.

The α-actinin-3 proteins regulate muscle function and are located in the Z-line of the fast skeletal muscle. A common null polymorphism of R577X in α-actinin-3 gene (ACTN3) results in its complete absence in fast-twitch muscles. The ACTN3 R577X polymorphism is associated with sprint/power performance in athletes. However, little is known about how this polymorphism impacts sports other than sprint/power-oriented sports in Japanese elite athletes. The aim of our study was to examine the association between ACTN3 R577X polymorphism and elite athlete status in various sports categorized as power/sprint, endurance, artistic, martial arts, and ball game sports. The subjects included 906 Japanese elite athletes and 649 Japanese controls. We analysed the genotype frequency of the ACTN3 R577X polymorphism in sprint/power (n = 120), endurance (n = 150), artistic (n = 45), martial arts (n = 94), and ball game (n = 497) sports athletes. A higher number of sprint/power athletes were R allele carriers compared to the controls, and the endurance and artistic athletes (OR = 1.69, 1.83, and 2.36, 95% CI: 1.02–2.79, 1.02–3.31, and 1.08–5.13, respectively). The frequency of RR genotype was higher in sprint/power, martial arts, and ball game sports athletes (OR = 1.61, 1.84, and 1.39, 95% CI: 1.04–2.50, 1.11–2.95, and 1.05–1.83, respectively) compared to control. Furthermore, there is a significant linear trend with increasing R allele according to athletic status (P for trend < 0.05). The ACTN3 R allele is positively associated with sports performance requiring explosive power such as sprint/power, martial arts, and ball game sports categories.

Age-related decreases in executive function and an increase in arterial stiffness and plasma homocysteine levels are related to the risk of dementia. However, the association between executive function, arterial stiffness, and homocysteine levels remains unclear. This study aimed to investigate the relationship between executive function, arterial stiffness, and plasma homocysteine in 82 middle-aged and older women. The Stroop interference time, Brachial-ankle Pulse Wave Velocity (baPWV), and plasma homocysteine concentration were collected. The correlation analyses revealed that the Stroop interference time was significantly correlated with plasma homocysteine ( r = 0.40, p < 0.001) and baPWV ( r = 0.38, p = 0.001). In addition, plasma homocysteine levels were significantly correlated with baPWV ( r = 0.48, p < 0.001). In the mediated analyses, the plasma homocysteine level directly ( β = 0.24; p = 0.037) and indirectly ( β = 0.12, 95% confidence interval [0.007, 0.238]) affected the Stroop interference time. These results suggest that higher plasma homocysteine levels are associated with a decline in executive function mediated by higher artery stiffness in middle-aged and older women.

Background The underlying mechanism linking the decline in exercise capacity with renal dysfunction remains unclear. Urinary liver-type fatty acid-binding protein (L-FABP) levels reflect the degree of peritubular capillary blood flow, an important factor for renal dysfunction with aging. The aim of this study was to examine the relationship between exercise capacity and urinary L-FABP levels. Methods This was a cross-sectional study of 187 middle-aged and older individuals (aged 50–83 years) without chronic kidney disease (CKD). We assessed urinary L-FABP levels, peak oxygen consumption ( V ˙ O 2peak ), and grip strength. Results Urinary L-FABP levels inversely correlated with both V ˙ O 2peak ( r s  = −0.349) and grip strength ( r s  = −0.485). When the participants were divided into four groups according to the median values of aerobic fitness and muscular strength ( V ˙ O 2peak and grip strength), urinary L-FABP levels were the highest in participants with lower levels of aerobic fitness and muscular strength (2.95 ± 1.43 μg/g creatinine) and the lowest in the participants with higher levels of aerobic fitness and muscular strength (1.33 ± 0.76 μg/g creatinine). The difference between the two groups was significant ( P  < 0.001). Conclusion Our results demonstrate that both V ˙ O 2peak and grip strength were inversely associated with urinary L-FABP levels in middle-aged and older individuals without CKD. This suggests that a decline in exercise capacity is associated with a reduction in peritubular capillary blood flow, providing a novel insight into the underlying mechanism linking the decline in exercise capacity to the development of renal dysfunction.

Background Mental stress is a risk factor for cardiovascular disease. However, little is known about the impact of mental stress on arterial function in middle-aged and older adults. Objective This study is aimed to investigate the association between mental stress and arterial function in this population. Methods A total of 156 healthy middle-aged and older adults (aged 50–79 years) participated in this study. Mental stress was evaluated by the General Health Questionnaire (GHQ), and arterial stiffness was measured by the Carotid-femoral Pulse Wave Velocity (cfPWV). Results cfPWV was significantly correlated with the GHQ score, even after adjustment for age, sex, body mass index, and cholesterol, triglyceride, and glucose. Multiple regression analysis further indicated that GHQ score was a significantly independent determinant of cfPWV ( p < 0.05). Conclusion GHQ is positively associated with arterial stiffness, independent of the potential confounding factors in healthy middle-aged and older adults.