Morphological variation and phylogeny of Karenia selliformis (Gymnodiniales, Dinophyceae) in an intensive cold-water algal bloom in eastern Hokkaido, Japan.

Harmful algal blooms responsible for mass mortalities of marine organisms have been rare in Hokkaido, northern Japan, although fish-killing blooms have been frequently reported from western Japanese coasts. In September-November 2021, a huge and prolonged cold-water bloom occurred along the Pacific coast of eastern Hokkaido, and was associated with intensive mortalities of sea urchin, fish, octopus, shellfish, etc. In this study, morphology and phylogeny of the dominant and co-occurring unarmored dinoflagellates of the Kareniaceae in the bloom were examined by using light microscopy, scanning electron microscopy and molecular phylogeny inferred from ITS and LSU rDNA (D1-D3) sequences. Morphological observation and molecular phylogeny showed that the dominant species was Karenia selliformis, with co-occurrences of other kareniacean dinoflagellates, Kr. longicanalis, Kr. mikimotoi, Karlodinium sp., Takayama cf. acrotrocha, Takayama tuberculata and Takayama sp. The typical cell forms of Kr. selliformis in the bloom were discoid, dorsoventrally flattened, and 35.3-43.6 (39.4  ±  2.1) µm in length, which was larger than the cell sizes in previous reports. Transparent cells of Kr. selliformis, lacking chloroplasts or having a few shrunken chloroplasts and oil droplets, were also found. Cells of Kr. selliformis showed morphological variation, but the species could be distinguished from other co-occurring Karenia species by the nucleus positioned in the hypocone and chloroplasts numerous (46-105) in number and small (2.9-4.6 µm) in diameter. Cell density of Kr. selliformis exceeding 100 cells mL-1 was recorded in the temperature range of 9.8-17.6 °C. The rDNA sequences determined from Kr. selliformis in the blooms of Hokkaido, Japan in 2021 were identical to those from the bloom in Kamchatka, Russia in 2020.

Decreased muscle-derived musclin by chronic resistance exercise is associated with improved insulin resistance in rats with type 2 diabetes.

Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle-derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter-4 (GLUT-4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. This study aimed to clarify whether decreased muscle-derived musclin secretion in chronic resistance exercise is involved in the improvement of insulin resistance via the GLUT-4 signaling pathway in rats with type 2 diabetes. Male, 20-week-old, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two groups: sedentary control (OLETF-Con) and chronic resistance exercise (OLETF-RT; climbing a ladder three times a week on alternate days for 8 weeks), whereas Long-Evans Tokushima Otsuka rats were used as the nondiabetic sedentary control group. OLETF-Con rats showed increased fasting glucose levels, decreased insulin sensitivity index (QUICKI), muscle GLUT-4 translocation, and protein kinase B (Akt) phosphorylation, and concomitantly increased muscle musclin expression. In contrast, OLETF-RT rats significantly reduced muscle musclin expression, improved hyperglycemia, and QUICKI through an accelerated muscle GLUT-4/Akt signaling pathway. Moreover, chronic resistance exercise-induced reduction of muscle musclin was correlated with changes in fasting glucose, QUICKI, GLUT-4 translocation, and Akt phosphorylation. These findings suggest that the reduction in muscle-derived musclin production by chronic resistance exercise may be involved in improved insulin resistance in rats with type 2 diabetes.

Aerobic Exercise Restores Aging-Associated Reductions in Arterial Adropin Levels and Improves Adropin-Induced Nitric Oxide-Dependent Vasorelaxation.

Background Adropin is a peptide hormone that promotes nitric oxide (NO) production via activation of endothelial NO synthase (eNOS) in endothelial cells. Its circulating levels are reduced with aging and increased with aerobic exercise training (AT). Using a mouse model, we hypothesized that AT restores aging-associated reductions in arterial and circulating adropin and improves adropin-induced NO-dependent vasorelaxation. Further, we hypothesized these findings would be consistent with data obtained in elderly humans. Methods and Results In the animal study, 50-week-old SAMP1 male mice that underwent 12 weeks of voluntary wheel running, or kept sedentary, were studied. A separate cohort of 25-week-old SAMP1 male mice were used as a mature adult sedentary group. In the human study, 14 healthy elderly subjects completed an 8-week AT program consisting of 45 minutes of cycling 3 days/week. In mice, we show that advanced age is associated with a decline in arterial and circulating levels of adropin along with deterioration of endothelial function, arterial NO production, and adropin-induced vasodilation. All these defects were restored by AT. Moreover, AT-induced increases in arterial adropin were correlated with increases in arterial eNOS phosphorylation and NO production. Consistently with these findings in mice, AT in elderly subjects enhanced circulating adropin levels and these effects were correlated with increases in circulating nitrite/nitrate (NOx) and endothelial function. Conclusions Changes in arterial adropin that occur with age or AT relate to alterations in endothelial function and NO production, supporting the notion that adropin should be considered a therapeutic target for vascular aging. Registration URL: https://www.umin.ac.jp; Unique identifier: UMIN000035520.

Acute effect of passive one-legged intermittent static stretching on regional blood flow in young men.

PURPOSE: Passive stretching reduces stiffness in the lower limb arteries of the stretched limb. To address this physiological mechanism, we measured the change in shear rate in the posterior tibial artery during a single bout of one-legged passive calf stretching compared with that in the non-stretched leg. METHODS: The diameter, mean blood velocity, blood flow, and shear rate in the posterior tibial artery were measured using Doppler ultrasound before (baseline), during, and after a one-legged passive intermittent calf stretching procedure (six repetitions of 30-s static stretch with 10-s relaxation) in nine healthy young men. RESULTS: In the posterior tibial artery of the stretched leg, the arterial diameter significantly decreased from baseline during the stretching period (baseline vs. stretching period of the 6th set, 0.19 ± 0.01 vs. 0.18 ± 0.01 cm, P < 0.05) without any change in shear rate and mean blood velocity. In contrast, during the relaxation period, the mean blood velocity (baseline vs. relaxation period of the 5th set, 2.98 ± 0.54 vs. 6.25 ± 1.48 cm/s) increased, and consequently, the shear rate (baseline vs. relaxation period of the 5th set, 66.75 ± 15.39 vs. 122.85 ± 29.40 s-1) increased (each P < 0.01); however, there was no change in arterial diameter. In contrast, these values in the non-stretched leg were unchanged at all-time points. CONCLUSIONS: The stretching procedure increased the shear rate in the peripheral artery of the stretched leg during the relaxation period. This finding indicates that the local hemodynamic response (possibly through endothelial function), resulting from an increase in shear stress, may contribute to stretching-induced attenuation of local arterial stiffness.

Effects of combined exercise training and Chlorella intake on vasorelaxation mediated by nitric oxide in aged mice.

Chronic Chlorella intake and aerobic exercise training reduce arterial stiffness and increase circulating nitric oxide (NO) levels, which has beneficial effects. This study aimed to clarify the combined aortic NO-mediated effects of chronic Chlorella intake and aerobic exercise training on endothelial vasorelaxation in aged mice. In this study, 38-week-old male senescence-accelerated mouse prone 1 (SAMP1) mice were divided into aged sedentary control (Con), aerobic exercise training (AT; voluntary wheel running for 12 weeks), Chlorella intake (CH; 0.5% Chlorella powder in normal diet), and AT and CH combined (AT+CH) groups. Endothelium-dependent vasorelaxation by addition of acetylcholine to the isolated mouse aortic rings was significantly higher in the AT, CH, and AT+CH groups than in the Con group; a significantly greater effect was seen in the AT+CH group than in the AT and CH groups. Similarly, plasma and arterial nitrite/nitrate levels and arterial endothelial NO synthase phosphorylation were significantly higher in the AT, CH, and AT+CH groups than in the Con group; the AT+CH group had higher values than the AT and CH groups. Thus, chronic Chlorella intake combined with aerobic exercise training had pronounced effects on endothelial vasorelaxation in aged mice via an additive increase in arterial NO production. Novelty: Endothelium-dependent vasorelaxation was improved by Chlorella intake and exercise. Chlorella intake and exercise increased arterial Akt/eNOS/NO signaling. This combination approach further improved vasorelaxation via arterial NO production.

Effects of Dioscorea esculenta intake with resistance training on muscle hypertrophy and strength in sprint athletes.

Androgen hormones are important compounds related to body composition and exercise performance in athletes. The intake of Dioscorea esculenta, known as lesser yam, contains diosgenin and resistance training have been shown to normalize the secretion of androgen hormones. This study aimed to clarify the level of androgen hormone secretion and the effects of Dioscorea esculenta intake with resistance training on muscle hypertrophy and strength in athletes. First, in a cross-sectional study, we compared the serum androgen hormone [dehydroepiandrosterone (DHEA), testosterone, and 5α-dihydrotestosterone (DHT)] levels between sprint athletes (n = 15) and non-athletes (n = 15). Second, in an 8-week intervention study, sprint athletes were randomly divided into 2 groups: resistance training with placebo (n = 8) or with Dioscorea esculenta (2,000 mg/day) intake (n = 7). The serum DHEA, free testosterone, and DHT levels were lower in athletes than in non-athletes. Dioscorea esculenta intake combined with resistance training increased the arm fat-free mass, the 1 repetition maximum of deadlift and snatch, and the serum DHEA, free testosterone, and DHT levels, compared with resistance training and placebo intake. The results suggested that Dioscorea esculenta intake combined with resistance training has further effects on muscle hypertrophy and strength in athletes by restoring secretion of androgen hormones.

Resistance exercise-induced increase in muscle 5α-dihydrotestosterone contributes to the activation of muscle Akt/mTOR/p70S6K- and Akt/AS160/GLUT4-signaling pathways in type 2 diabetic rats.

Effects of increase in muscle 5α-dihydrotestosterone (DHT) levels caused by resistance exercise on regulation of mammalian target of rapamycin (mTOR)- and glucose transporter 4 (GLUT4)-signaling pathways in type 2 diabetic rats were assessed. Twenty-week-old type 2 diabetic rats were randomly divided into the resting control, immediately, 1 hour, or 3 hours after resistance exercise, with or without the pretreatment of 5α-reductase inhibitor. Immediately or 1 hour after exercise, levels of 5α-reductase and DHT as well as phosphorylation levels of AMP-activated protein kinase (AMPK), TBC1 domain family member 1 (TBC1D1), and protein kinase B (Akt) in muscle were significantly elevated. Phosphorylation of muscle Akt substrate of 160 kDa (AS160) and translocation levels of GLUT4 at 1 and 3 hours after resistance exercise were significantly elevated. Additionally, resistance exercise significantly activated the phosphorylation of muscle mTOR immediately, and at 1 and 3 hours and of p70 ribosomal S6 kinase (p70S6K) at 1 and 3 hours. However, pretreatment with the 5α-reductase inhibitor significantly attenuated the exercise-induced activation of Akt/mTOR/p70S6K and Akt/AS160/GLUT4 signaling, but did not affect AMPK/TBC1D1/GLUT4 signaling. These findings suggest that resistance exercise-induced increase in muscle DHT synthesis may contribute to activation of Akt/mTOR/p70S6K- and Akt/AS160/GLUT4 signaling pathways in type 2 diabetic rats.

Conduction Velocity of Muscle Action Potential of Knee Extensor Muscle During Evoked and Voluntary Contractions After Exhaustive Leg Pedaling Exercise.

PURPOSE: Muscle fiber conduction velocity (CV) has been developed to estimate neuromuscular fatigue and measured during voluntary (VC) and electrically evoked (EC) contractions. Since CV during VC and EC reflect different physiological phenomena, the two parameters would show inconsistent changes under the conditions of neuromuscular fatigue. We investigated the time-course changes of CV during EC and VC after fatiguing exercise. METHODS: In 14 young males, maximal voluntary contraction (MVC) of knee extensor muscles, CV during electrical stimulation (CV-EC) and MVC (CV-VC) were measured before and immediately, 30 min, 60 min, 120 min, and 24 h after exhaustive leg pedaling exercise. RESULTS: CV-EC significantly increased immediately after the fatiguing exercise (p < 0.05) and had a significant negative correlation with MVC in merged data from all time-periods (r = -0.511, p < 0.001). CV-VC significantly decreased 30, 60, and 120 min after the fatiguing exercise (p < 0.05) and did not show any correlations with MVC (p > 0.05). CONCLUSION: These results suggest that CV during EC and VC exhibits different time-course changes, and that CV during EC may be appropriate to estimate the degree of neuromuscular fatigue after fatiguing pedaling exercise.

Increased serum salusin-α by aerobic exercise training correlates with improvements in arterial stiffness in middle-aged and older adults.

Aging causes arterial stiffening which can be mitigated by increased physical activity. Although low circulating levels of salusin-α are associated with cardiovascular disease, whether salusin-α decreases with aging and whether the reduced arterial stiffening occurring with exercise training is associated with increased serum salusin-α is unknown. Herein we assessed carotid-femoral pulse wave velocity (cfPWV), systolic (SBP) and diastolic (DBP) blood pressures in a cross-sectional study that compared young (20-39-year-old, n=45) versus middle-aged and older (40-80-year-old, n=60) subjects. We also performed an interventional study in which 36 young and 40 middle-aged and older subjects underwent eight weeks of aerobic exercise training. In the cross-sectional study, serum salusin-α levels were lesser in middle-aged and older subjects compared to young individuals and negatively correlated with age, SBP, DBP, or cfPWV. In the interventional study, exercise training increased serum salusin-α in middle-aged and older subjects. Notably, negative correlations were noted between the exercise training-induced changes in serum salusin-α and cfPWV, SBP and DBP. Results indicate that advanced age associates with low circulating salusin-α, the levels of which can be augmented by exercise training. Importantly, increased serum salusin-α with exercise correlates with improvements in arterial stiffness and a reduction in blood pressure.

Aerobic exercise training-induced irisin secretion is associated with the reduction of arterial stiffness via nitric oxide production in adults with obesity.

This study aimed to clarify whether muscle-derived irisin secretion induced by aerobic exercise training is involved in reduction of arterial stiffness via arterial nitric oxide (NO) productivity in obesity. In animal study, 16 Otsuka Long-Evans Tokushima Fatty (OLETF) rats with obesity were randomly divided into 2 groups: sedentary control (OLETF-CON) and 8-week aerobic treadmill training (OLETF-EX) groups. In human study, 15 subjects with obesity completed 8-week aerobic exercise training for 45 min at 60%-70% peak oxygen uptake intensity for 3 days/week. As a result of animal study, carotid-femoral pulse wave velocity (cfPWV) was decreased, and arterial phosphorylation levels of AMP-activated protein kinase (AMPK), protein kinase B (Akt), and endothelial NO synthase (eNOS), circulating levels of nitrite/nitrate (NOx) and irisin, and muscle messenger RNA expression of fibronectin type III domain containing 5 (Fndc5) were increased in the OLETF-EX group compared with OLETF-CON group. In a human study, regular aerobic exercise reduced cfPWV and elevated circulating levels of NOx and irisin. Furthermore, change in circulating irisin levels by regular exercise was positively correlated with circulating NOx levels and was negatively correlated with cfPWV. Thus, aerobic exercise training-induced increase in irisin secretion may be related to reduction of arterial stiffness achieved by NO production via activated arterial AMPK-Akt-eNOS signaling pathway in obesity. Novelty Aerobic exercise training promoted irisin secretion with upregulation of muscle Fndc5 gene expression in rats with obesity. Irisin affected the activation of arterial AMPK-Akt-eNOS signaling by aerobic exercise training. Increased serum irisin level by aerobic exercise training was associated with reduction of arterial stiffness in obese adults.

Sparassis crispa Intake Improves the Reduced Lipopolysaccharide-Induced TNF-α Production That Occurs upon Exhaustive Exercise in Mice.

Our previous study showed that lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production is inhibited by acute exhaustive exercise in mice, leading to transient immunodepression after exercise. Sparassis crispa (SC), an edible mushroom, has immunopotentiative properties. This study aimed to clarify the effects of SC intake on reduced LPS-induced TNF-α production upon exhaustive exercise in mice. Male C3H/HeN mice were randomly divided into three groups: normal chow intake + resting sedentary, normal chow intake + acute exhaustive treadmill running exercise, and SC intake (chow containing 5% SC powder for 8 weeks) + the exhaustive exercise groups. Each group was injected with LPS immediately after the exhaustive exercise or rest. Plasma and tissue TNF-α levels were significantly decreased by exhaustive exercise. However, this reduction of the TNF-α level was partially attenuated in the plasma and small intestine by SC intake. Although levels of TLR4 and MyD88 protein expression were significantly decreased in tissues by exhaustive exercise, the reduction of TLR4 and MyD88 levels in the small intestine was partially attenuated by SC intake. These results suggest that SC intake attenuates exhaustive exercise-induced reduction of TNF-α production via the retention of TLR4 and MyD88 expression in the small intestine.

Aging-induced elevation in circulating complement C1q level is associated with arterial stiffness.

Inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) are candidate blood biomarkers of cardiovascular disease (CVD). However, no consensus has been reached on the relationships between aging-induced secretion of cytokines and CVD risk. Complement C1q (C1q) secretion increases with aging, and C1q induces proliferation of vascular smooth muscle cells. Therefore, the secretion of C1q with aging may be a risk factor of CVD and reflect arterial stiffening and blood pressures. This study aimed to clarify whether aging-induced increase in serum C1q, TNF-α, and IL-6 levels are associated with arterial stiffness. One hundred twenty-seven healthy subjects participated in this study. Serum C1q, TNF-α, and IL-6 levels and carotid-femoral pulse wave velocity (cfPWV; arterial stiffness index) in middle-aged and older subjects (≥40 years) were significantly increased as compared with those in young subjects (<40 years; P < 0.05). The serum C1q, TNF-α, and IL-6 levels positively correlated with cfPWV (P < 0.05). Furthermore, C1q level contributed independently to the cfPWV variation after adjustment for 11 confounders. Moreover, serum C1q level is associated with cfPWV regardless of sex, but these relationships with TNF-α or IL-6 differed between sex. Importantly, cfPWV gradually increased from the age of 30 years, with simultaneous increase in circulating C1q level. However, TNF-α and IL-6 levels increased after age 50 years, later than the increase in C1q. These results suggest that serum C1q level may reflect the elevation of arterial stiffness that occurs with advancing age and has a potential as a novel biomarker of arterial stiffness.

Effect of combination of chlorella intake and aerobic exercise training on glycemic control in type 2 diabetic rats.

OBJECTIVES: Chlorella is a type of unicellular green algae that contains various nutrients. Habitual exercise and chlorella treatment can improve insulin resistance in obese or diabetic animal models. However, the additive effects of combined chlorella intake and aerobic exercise training remain unclear. The aim of this study was to investigate whether a combination of chlorella intake and aerobic exercise training would produce greater effects on improving glycemic control in rats with type 2 diabetes. METHODS: Twenty-wk-old male rats with type 2 diabetes (Otsuka Long-Evans Tokushima Fatty [OLETF] rats) were randomly divided into four groups: sedentary control, aerobic exercise training (treadmill running for 1 h, 25m/min, 5 d/wk), chlorella intake (0.5% chlorella powder in normal diet), or combination of aerobic exercise training and chlorella intake for 8 wk (n = 7 per group). RESULTS: Chlorella intake and aerobic exercise training significantly decreased fasting blood glucose, insulin levels, and total glucose area under the curve during the oral glucose tolerance test and increased the insulin sensitivity index concomitant with muscle phosphatidylinositol-3 kinase (PI3K) activity, protein kinase B (Akt) phosphorylation, and glucose transporter 4 (GLUT4) translocation levels. Furthermore, a combination of chlorella intake and aerobic exercise training significantly further improved these effects compared with aerobic exercise training or chlorella intake alone. CONCLUSIONS: These results suggested that chlorella intake combined with aerobic exercise training had more pronounced effects on the improvement of glycemic control via further activation of muscle PI3K/Akt/GLUT4 signaling in rats with type 2 diabetes.

Detailed insights into pan-European population structure and inbreeding in wild and hatchery Pacific oysters (Crassostrea gigas) revealed by genome-wide SNP data.

Cultivated bivalves are important not only because of their economic value, but also due to their impacts on natural ecosystems. The Pacific oyster (Crassostrea gigas) is the world's most heavily cultivated shellfish species and has been introduced to all continents except Antarctica for aquaculture. We therefore used a medium-density single nucleotide polymorphism (SNP) array to investigate the genetic structure of this species in Europe, where it was introduced during the 1960s and has since become a prolific invader of coastal ecosystems across the continent. We analyzed 21,499 polymorphic SNPs in 232 individuals from 23 localities spanning a latitudinal cline from Portugal to Norway and including the source populations of Japan and Canada. We confirmed the results of previous studies by finding clear support for a southern and a northern group, with the former being indistinguishable from the source populations indicating the absence of a pronounced founder effect. We furthermore conducted a large-scale comparison of oysters sampled from the wild and from hatcheries to reveal substantial genetic differences including significantly higher levels of inbreeding in some but not all of the sampled hatchery cohorts. These findings were confirmed by a smaller but representative SNP dataset generated using restriction site-associated DNA sequencing. We therefore conclude that genomic approaches can generate increasingly detailed insights into the genetics of wild and hatchery produced Pacific oysters.

Gene Expression Profiles for Macrophage in Tissues in Response to Different Exercise Training Protocols in Senescence Mice.

Age-induced chronic inflammation is prevented by aerobic and resistance exercise training. However, the effects of the mechanism of exercise on chronic inflammation in each tissue remains unclear. The aim of this study was to investigate the effects of resistance and aerobic training on gene expression profiles for macrophage infiltration and polarization (M1/M2 ratio) with chronic inflammation in various tissues of aged model mice. Male 38-week-old SAMP1 (senescence-accelerated prone mouse 1) mice were randomly divided into three groups-sedentary (Aged-Sed-SAMP1), aerobic training (Aged-AT-SAMP1; voluntary running), and resistance training-for 12 weeks (Aged-RT-SAMP1; climbing ladder). Resistance and aerobic exercise training prevented an increase in circulating TNF-α levels (a marker of systemic inflammation) in aged SAMP1 mice, along with decreases in tissue inflammatory cytokine (TNF-α and IL-1ß) mRNA expression in the heart, liver, small intestine, brain, aorta, adipose, and skeletal muscle, but it did not change the levels in the lung, spleen, and large intestine. Moreover, resistance and aerobic exercise training attenuated increases in F4/80 mRNA expression (macrophage infiltration), the ratio of CD11c/CD163 mRNA expression (M1/M2 macrophage polarization), and MCP-1 mRNA expression (chemokine: a regulator of chronic inflammation) in the chronic inflamed tissues of aged SAMP1 mice. These results suggested that resistance and aerobic exercise training-induced changes in gene expression for macrophage infiltration and polarization in various tissues might be involved in the prevention of age-related tissue chronic inflammation, and lead to a reduction of the increase in circulating TNF-α levels, as a marker of systemic inflammation, in aged SAMP1 mice.

Gene expression profile of muscle adaptation to high-intensity intermittent exercise training in young men.

High-intensity intermittent exercise training (HIIT) has been proposed as an effective approach for improving both, the aerobic and anaerobic exercise capacity. However, the detailed molecular response of the skeletal muscle to HIIT remains unknown. We examined the effects of the HIIT on the global gene expression in the human skeletal muscle. Eleven young healthy men participated in the study and completed a 6-week HIIT program involving exhaustive 6-7 sets of 20-s cycling periods with 10-s rests. In addition to determining the maximal oxygen uptake ([Formula: see text]), maximal accumulated oxygen deficit, and thigh muscle cross-sectional area (CSA), muscle biopsy samples were obtained from the vastus lateralis before and after the training to analyse the skeletal muscle transcriptome. The HIIT program significantly increased the [Formula: see text], maximal accumulated oxygen deficit, and thigh muscle CSA. The expression of 79 genes was significantly elevated (fold-change >1.2), and that of 73 genes was significantly reduced (fold-change <0.8) after HIIT. Gene ontology analysis of the up-regulated genes revealed that the significantly enriched categories were "glucose metabolism", "extracellular matrix", "angiogenesis", and "mitochondrial membrane". By providing information about a set of genes in the human skeletal muscle that responds to the HIIT, the study provided insight into the mechanism of skeletal muscle adaptation to HIIT.

Resistance training prevents muscle fibrosis and atrophy via down-regulation of C1q-induced Wnt signaling in senescent mice.

Increased complement component 1q (C1q) secretion with aging leads to muscle fibrosis and atrophy whereas resistance training attenuates circulating C1q levels. This study aimed to clarify whether resistance exercise-induced reduction of C1q secretion contributes to the inhibition of fibrosis and atrophy in aged muscles. Young (13-wk-old) and aged (38-wk-old) senescence-accelerated mouse prone 1 mice were randomly assigned to one of 4 groups: a young or aged sedentary control group, or a young or aged resistance training (climbing a ladder 3 d/wk for 12 wk) group. We found that resistance training ameliorated muscle fibrosis and atrophy in aged mice, concomitant with decreased circulating and muscle C1q levels and attenuated activation of muscle Wnt signaling (glycogen synthase kinase ß/ß-catenin), including ß-catenin in satellite (Pax7+/DAPI+) and fibroblast (vimentin+/DAPI+) cells. Furthermore, during muscle regeneration after mice were injured by cardiotoxin injection, we observed a reduction in circulating C1q levels, the inhibition of muscle fibrosis and repair, and decreased in the activation of muscle cytoplasmic and nuclear ß-catenin in aged mice from the resistance training group, but these effects were cancelled by a single preadministration of exogenous recombinant C1q. In addition, resistance training attenuated aging-related muscle loss concomitant with decreased expression of both muscle ring-finger protein 1 and muscle atrophy F-box in the muscle. Thus, resistance training-induced changes in circulating C1q levels may contribute to the prevention of muscle fibrosis and atrophy via muscle Wnt signaling in senescent mice.-Horii, N., Uchida, M., Hasegawa, N., Fujie, S., Oyanagi, E., Yano, H., Hashimoto, T., Iemitsu, M. Resistance training prevents muscle fibrosis and atrophy via down-regulation of C1q-induced Wnt signaling in senescent mice.

Effects of Different Exercise Modes on Arterial Stiffness and Nitric Oxide Synthesis.

PURPOSE: Aerobic training (AT) and high-intensity intermittent training (HIIT) reduce arterial stiffness, whereas resistance training (RT) induces deterioration of or no change in arterial stiffness. However, the molecular mechanism of these effects of different exercise modes remains unclear. This study aimed to clarify the difference of different exercise effects on endothelial nitric oxide synthase (eNOS) signaling pathway and arterial stiffness in rats and humans. METHODS: In the animal study, forty 10-wk-old male Sprague-Dawley rats were randomly divided into four groups: sedentary control (CON), AT (treadmill running, 60 min at 30 m·min, 5 d·wk for 8 wk), RT (ladder climbing, 8-10 sets per day, 3 d·wk for 8 wk), and HIIT (14 repeats of 20-s swimming session with 10-s pause between sessions, 4 d·wk for 6 wk from 12-wk-old) groups (n = 10 in each group). In the human study, we confirmed the effects of 6-wk HIIT and 8-wk AT interventions on central arterial stiffness and plasma nitrite/nitrate level in untrained healthy young men in randomized controlled trial (HIIT, AT, and CON; n = 7 in each group). RESULTS: In the animal study, the effect on aortic pulse wave velocity (PWV), as an index of central arterial stiffness, after HIIT was the same as the decrease in aortic PWV and increase in arterial eNOS/Akt phosphorylation after AT, which was not changed by RT. A negative correlation between aortic PWV and eNOS phosphorylation was observed (r = -0.38, P < 0.05). In the human study, HIIT- and AT-induced changes in carotid-femoral PWV (HIIT -115.3 ± 63.4 and AT -157.7 ± 45.7 vs CON 71.3 ± 61.1 m·s, each P < 0.05) decreased, and plasma nitrite/nitrate level increased compared with those in CON. CONCLUSIONS: HIIT may reduce central arterial stiffness via the increase in aortic nitric oxide bioavailability despite it being done in a short time and short term and has the same effects as AT.

Aerobic exercise training-induced changes in serum C1q/TNF-related protein levels are associated with reduced arterial stiffness in middle-aged and older adults.

Adiponectin regulates endothelial nitric oxide synthase in endothelial cells, and body fat loss by aerobic exercise training promotes adiponectin secretion. Recently, C1q/tumor necrosis factor-related proteins (CTRPs) have been identified as novel adipokines and are paralogs of adiponectin, but the association between exercise training-induced reduction of arterial stiffness and circulating CTRPs levels remains unclear. This study aimed to clarify whether the reduction of arterial stiffness in middle-aged and older adults is associated with the change in serum levels of CTRPs induced by exercise training. A total of 52 middle-aged and older participants were randomly divided into two groups: a training group ( n = 26) and a sedentary control group ( n = 26). Participants in the training group completed 8 wk of aerobic exercise training (60-70% peak oxygen uptake for 45 min, 3 days/wk). The reduction of percent whole body fat, abdominal visceral fat area, and carotid-femoral pulse-wave velocity (cfPWV) was significantly greater in the training group than in the control group ( P < 0.05). Moreover, the increase in serum adiponectin, CTRP3, and CTRP5 from baseline to 8 wk was significantly higher in the training group compared with the control group ( P < 0.05). Additionally, the training-induced change in cfPWV was negatively correlated with the training-induced change in serum adiponectin, CTRP3, and CTRP5 levels ( r = -0.51, r = -0.48, r = -0.42, respectively, P < 0.05), and increased plasma nitrite/nitrate level by exercise training was correlated only with adiponectin levels ( r = 0.41, P < 0.05). These results suggest that the exercise training-induced increase in serum CTRPs levels may be associated with the reduction of arterial stiffness in middle-aged and older adults.

Acute effect of stretching one leg on regional arterial stiffness in young men.

PURPOSE: Our previous study demonstrated that a single bout of stretching exercises acutely reduced arterial stiffness. We hypothesized that this acute vascular response is due to regional mechanical stimulation of the peripheral arteries. To test this hypothesis, we examined the effect of a single bout of passive one leg stretching on arterial stiffness, comparing the stretched and the non-stretched leg in the same subject. METHODS: Twenty-five healthy young men (20.9 ± 0.3 years, 172.5 ± 1.4 cm, 64.1 ± 1.2 kg) volunteered for the study. Subjects underwent a passive calf stretching on one leg (six repetitions of 30-s static stretch with a 10-s recovery). Pulse wave velocity (PWV, an index of arterial stiffness), blood pressure (BP), and heart rate (HR) were measured before and immediately, 15, and 30 min after the stretching. RESULTS: Femoral-ankle PWV (faPWV) in the stretched leg was significantly decreased from baseline (835.0 ± 15.9 cm/s) to immediately (802.9 ± 16.8 cm/s, P < 0.01) and 15 min (810.5 ± 16.0 cm/s, P < 0.01) after the stretching, despite no changes in systolic and diastolic BP, or HR. However, faPWV in the non-stretched leg was not significantly altered at any time. Brachial-ankle PWV (baPWV) also showed similar responses with faPWV, but this response was not significant. Additionally, the passive stretching did not alter carotid-femoral PWV (cfPWV). CONCLUSIONS: These results suggest that mechanical stimulation to peripheral arteries as induced by static passive stretch may modulate arterial wall properties directly, rather than resulting in a systemic effect.