Ablation of specific insulin-like growth factor I forms reveals the importance of cleavage for regenerative capacity and glycosylation for skeletal muscle storage.

Insulin-like growth factor-I (IGF-I) facilitates mitotic and anabolic actions in all tissues. In skeletal muscle, IGF-I can promote growth and resolution of damage by promoting satellite cell proliferation and differentiation, suppressing inflammation, and enhancing fiber formation. While the most well-characterized form of IGF-I is the mature protein, alternative splicing and post-translational modification complexity lead to several additional forms of IGF-I. Previous studies showed muscle efficiently stores glycosylated pro-IGF-I. However, non-glycosylated forms display more efficient IGF-I receptor activation in vitro, suggesting that the removal of the glycosylated C terminus is a necessary step to enable increased activity. We employed CRISPR-Cas9 gene editing to ablate IGF-I glycosylation sites (2ND) or its cleavage site (3RA) in mice to determine the necessity of glycosylation or cleavage for IGF-I function in postnatal growth and during muscle regeneration. 3RA mice had the highest circulating and muscle IGF-I content, whereas 2ND mice had the lowest levels compared to wild-type mice. After weaning, 4-week-old 2ND mice exhibited higher body and skeletal muscle mass than other strains. However, by 16 weeks of age, muscle and body size differences disappeared. Even though 3RA mice had more IGF-I stored in muscle in homeostatic conditions, regeneration was delayed after cardiotoxin-induced injury, with prolonged necrosis most evident at 5 days post injury (dpi). In contrast, 2ND displayed improved regeneration with reduced necrosis, and greater fiber size and muscle mass at 11 and 21 dpi. Overall, these results demonstrate that while IGF-I glycosylation may be important for storage, cleavage is needed to enable IGF-I to be used for efficient activity in postnatal growth and following acute injury.

Influence of cardiorespiratory fitness and body composition on resting and post-exercise indices of vascular health in young adults.

Poor cardiorespiratory fitness may mediate vascular impairments at rest and following an acute bout of exercise in young healthy individuals. This study aimed to compare flow mediated dilation (FMD) and vascular augmentation index (AIx75) between young adults with low, moderate, and high levels of cardiorespiratory fitness before and after an acute bout of aerobic exercise. Forty-three participants (22 men; 21 women) between 18 and 29 years of age completed the study. Participants were classified into low, moderate, and high health-related cardiorespiratory fitness groups according to age- and sex-based relative maximal oxygen consumption (V˙O2 max) percentile rankings. FMD was performed using Doppler ultrasound and AIx75 was performed using pulse wave analysis at baseline and 60-min after a 30-min bout of treadmill running at 70% V˙O2 max. A significant interaction (p â€‹= â€‹0.047; ηp2 â€‹= â€‹0.142) was observed, with the moderate fitness group exhibiting a higher FMD post-exercise compared with baseline ([6.7% â€‹± â€‹3.1%] vs. [8.5% â€‹± â€‹2.8%], p â€‹= â€‹0.028; d â€‹= â€‹0.598). We found a significant main effect of group for AIx75 (p â€‹= â€‹0.023; ηp2 â€‹= â€‹0.168), with the high fitness group exhibiting lower AIx75 compared to low fitness group ([-10% â€‹± â€‹10%] vs. [2% â€‹± â€‹10%], respectively, p â€‹= â€‹0.019; g â€‹= â€‹1.07). This was eliminated after covarying for body fat percentage (p â€‹= â€‹0.489). Our findings suggest that resting FMD and AIx75 responses are not significantly influenced by cardiorespiratory fitness, but FMD recovery responses to exercise may be enhanced in individuals with moderate cardiorespiratory fitness levels.

Circulating immune cell populations at rest and in response to acute endurance exercise in young adults with cerebral palsy.

AIM: The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals. METHOD: Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19-38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20-40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups. RESULTS: Baseline levels of gamma delta (TCRγδ+) T-cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T-cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (-11.1%, p < 0.01), despite similar ratings of perceived exertion. INTERPRETATION: Elevated baseline TCRγδ+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise. WHAT THIS PAPER ADDS: TCRγδ+ T-cell baseline levels are elevated in adults with cerebral palsy (CP). The CD8+ T-cell response to exercise was blunted in adults with CP. Exercise intensity is decisive for CD8+ T-cell responses in individuals with CP.

High-intensity functional exercise does not cause persistent elevations in augmentation index in young men and women.

Elevations in central augmentation index (AIx) are predictive of cardiovascular disease. The objective of this study was to examine AIx immediately and 24 h following an acute bout of high-intensity functional training (HIFT) in apparently healthy young adults. A second aim compared the exercise-induced AIx recovery response between men and women. Thirty-two recreationally active younger adults (n = 16 men) were tested. Baseline central hemodynamic measures were assessed, followed by a single bout of bodyweight HIFT. The HIFT included 4 rounds of burpees, jump squats, split squats, and walking lunges. Assessments were repeated 5, 10, 15, and 24 h post-exercise. AIx was normalized to a heart rate of 75 bpm (AIx75). There was a significant main effect of time on AIx75 across all groups (P < 0.001) with AIx75 increasing at all acute time points compared with baseline and returning to resting values 24 h post-exercise. When examining sex differences after covarying for height and body fat percentage, the authors found no time × sex interaction (P = 0.62), or main effect for sex (P = 0.41), but the significant main effect of time remained (P < 0.001). The AIx75 response to HIFT follows a similar recovery pattern as previously studied modes of exercise with no residual effects 24 h later and no differences between men and women indicating no persistent cardiovascular strain in younger adults participating in this mode of exercise.