To elucidate the effects of endurance training on circulating irisin levels in young and middle-aged/older adults, and to determine the association between endurance training-induced alteration of irisin and reduction in body fat. Twenty-five healthy young (age 21 ± 1 years; 16 men, 9 women) and 28 healthy middle-aged/older adults (age 67 ± 8 years; 12 men, 16 women) participated in the study. Each age cohort was divided into two groups: the endurance-training group (14 young, 14 middle-aged/older) and the control group. Subjects in the training groups completed an 8-week endurance-training program (cycling at 60-70% peak oxygen uptake [ O_2peak] for 45 min, 3 days/week). Before and after the intervention, we evaluated serum irisin level, O_2peak, and body composition. The increase in O_2peak in the young and middle-aged/older training groups after the intervention period was significantly greater than those in the young and middle-aged/older control groups (P < 0.05). Serum irisin level was significantly increased in the middle-aged/older training group after the intervention period (P < 0.01), but not in the young training group. Furthermore, in the middle-aged/older training group, the endurance training-induced reduction in visceral adipose tissue area was negatively correlated with the change in serum irisin level (r = −0.54, P < 0.05). These results suggest a possible role for secreted irisin in the exercise-induced alteration of abdominal visceral fat in middle-aged and older adults.

Aging-induced arterial stiffening is reduced by aerobic exercise training, and elevated production of nitric oxide (NO) participates in this effect. Adropin is a regulator of endothelial NO synthase and NO release, and circulating adropin level decreases with age. However, the effect of habitual aerobic exercise on circulating adropin levels in healthy middle-aged and older adults remains unclear. We sought to determine whether serum adropin level is associated with exercise training-induced changes in arterial stiffness. First, in a cross-sectional study, we investigated the association between serum adropin level and both arterial stiffness and cardiorespiratory fitness in 80 healthy middle-aged and older subjects (65.6 ± 0.9 yr). Second, in an intervention study, we examined the effects of 8-wk aerobic exercise training on serum adropin level and arterial stiffness in 40 healthy middle-aged and older subjects (67.3 ± 1.0 yr) divided into two groups: aerobic exercise training and sedentary controls. In the cross-sectional study, serum adropin level was negatively correlated with carotid β-stiffness ( r = −0.437, P < 0.001) and positively correlated with plasma NOx level ( r = 0.493, P < 0.001) and cardiorespiratory fitness ( r = 0.457, P < 0.001). Serum adropin levels were elevated after the 8-wk aerobic exercise training intervention, and training-induced changes in serum adropin level were correlated with training-induced changes in carotid β-stiffness ( r = −0.399, P < 0.05) and plasma NOx level ( r = 0.623, P < 0.001). Thus the increase in adropin may participate in the exercise-induced reduction of arterial stiffness.

Aging-induced deterioration of arterial stiffness is decreased by regular exercise, and increased nitric oxide (NO) production participates in this effect. Apelin regulates endothelial NO synthase in endothelial cells, promoting NO production. However, the effect of aerobic exercise training on circulating apelin levels in healthy middle-aged and older adults remains unknown. Accordingly, this study aimed to clarify the effects of regular aerobic exercise on apelin concentrations in middle-aged and older adults. Thirty-four healthy middle-aged and older subjects (67.0 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed 8-week of aerobic exercise training (60–70% peak oxygen uptake [VO_2peak] for 45 min, 3 days/week). Before and after the intervention, we evaluated plasma apelin and nitrite/nitrate (NOx) concentrations, VO_2peak, and arterial stiffness index. In the training group, VO_2peak was significantly increased, and carotid β-stiffness was significantly decreased, after the intervention (P<0.05). Moreover, plasma apelin and NOx levels were significantly increased in the training group after the intervention (P<0.05). Additionally, there was a correlation between the training effects of plasma apelin levels and carotidβ-stiffness (r = −0.508, P = 0.032) and plasma NOx levels (r = 0.494, P = 0.037). By contrast, none of these parameters changed significantly in the control group. These results suggest that the increased in plasma apelin levels may be associated with exercise training-induced alternation of arterial stiffness in middle-aged and older adults.

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 β/β‐catenin), including β‐catenin in satellite ( P ax7 ⁺ /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 β‐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. FASEB J. 32, 3547–3559 (2018). www.fasebj.org

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 ( $${\dot{{\rm{V}}}{\rm{O}}}_{2{\rm{\max }}}$$V˙O2max ), 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 $${\dot{{\rm{V}}}{\rm{O}}}_{2{\rm{\max }}}$$V˙O2max , 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.