Volume 1, Issue 3-4

Objectives To investigate the impact of acute energetic stress (acute HIIE and fasting) on ERRγ , PPARβ , NR1D1 , NR4A1 , and TFEB in human skeletal muscle. Methods The current study performed secondary analyses using muscle biopsy samples from two previously published studies: study 1) leg muscle biopsies from nine men and eight women were obtained pre and 3 h following acute high-intensity interval cycling exercise (HIIE); study 2) leg muscle biopsies were obtained from nine men pre-, during, and post-an 8 h fast with or without 2 h of arm ergometer exercise. RT-PCR was performed on samples from each study to determine the mRNA expression of ERRγ , PPARβ , NR1D1 , NR4A1 , and TFEB . Additionally, we retrieved data from meta-analyzed human muscle gene expression using the publicly available database MetaMex. Results PGC-1α (p<0.01, d=1.98) and NR4A1 (p<0.01, d=1.36) mRNA expression significantly increased while TFEB (p≤0.05, d=0.70) decreased following HIIE. Significant decreases in NR4A1 and NR1D1 mRNA expression were observed following an 8 h fast. Our MetaMex analyses revealed significant increases (p<0.05) in PGC-1α and  NR4A1 expression following aerobic and resistance exercise, and in PPARβ expression following resistance exercise. Conclusions Our data indicate that acute HIIE stimulates increases in NR4A1 and PGC-1α and decreases in TFEB mRNA expression in human skeletal muscle. Additionally, a short term (8 h) fast reduced the mRNA expression of the transcriptional regulators NR4A1 and NR1D1  – potentially as a mechanism of decreasing mitochondrial biogenesis to reduce energy expenditure during a period of restricted energy availability.

Introduction Parkinson’s disease (PD) is a neurodegenerative disorder with increasing prevalence into older age. Aerobic exercise (AE) is the most commonly prescribed exercise for PD, although an optimal protocol is undefined. This umbrella review aimed to summarise and synthesize existent evidence regarding the effectiveness of AE on balance, gait, functional mobility, and QoL in people with PD. Content Six databases were searched for systematic reviews reporting the effects of AE on balance, gait, functional mobility, and QoL in people with PD from inception to June 2024. Quality of evidence was assessed using the AMSTAR-2 tool. From 4182 records, 17 systematic reviews were included for qualitative analysis. Most (n=12) were rated as critically low for methodological quality, with four rated low and one high. Moderate intensity was the most commonly investigated AE intensity (n=4), although almost half of the reviews (n=8) did not report intensity. AE protocols lasted from 1 to 64 weeks and 1 to 7 days per week. Session length was between 20 and 120 minutes. Reported outcomes included gait (n=15), QoL (n=14), balance (n=12), and functional mobility (n=7). AE does improve aspects of gait, balance, and functional mobility in PD; however it does not appear to improve QoL. Summary and Outlook AE is recommended as part of rehabilitation for people with PD. However, research exploring the efficacy of AE assesses multiple modalities with varied protocols. Further research is needed to identify AE protocols that will best alleviate the symptoms of PD, providing an evidence base for effective clinical translation.

Aging is associated with numerous physiological, musculoskeletal, and neurological impairments including a loss of muscle, strength, function, bone mineral, and cognition. Strength training is an effective intervention to counter these age-associated declines. In addition, creatine supplementation is purported to enhance strength training gains in lean tissue mass, muscular strength, and function. There is emerging evidence that creatine combined with strength training can alter bone geometry and cognitive performance. The purpose of this review is to update previous meta-analyses examining creatine combined with strength training on lean tissue mass and bone density compared to strength training and placebo. A secondary purpose was to explore the effects of creatine and strength training on cognition. Updated meta-analyses revealed that creatine enhances lean tissue mass (mean difference [MD]: 1.18 kg, 95 % CI: 0.70–1.67; p<0.00001) and upper body muscular strength (standard mean difference [SMD]: 0.24, 95 % CI: 0.05–0.43; p=0.02) compared to strength training and placebo. Creatine combined with strength training had no greater effects compared to strength training and placebo on lower body muscular strength (SMD: 0.17, 95 % CI: −0.03–0.38; p=0.09), whole-body (MD: −0.00 g cm −2 ; 95 % CI: −0.01–0.00, p=0.32), femoral neck (MD: −0.00 g cm −2 ; 95 % CI: −0.01–0.00, p=1.00), or lumbar bone mineral density (MD: 0.00 g cm −2 , 95 % CI: −0.01–0.01; p=045). There is preliminary evidence that combining strength training and creatine is an effective strategy to improve bone geometry in postmenopausal females and cognitive function in older adults. Overall, the combination of creatine and strength training has favorable effects on lean tissue mass and upper body strength. In contrast, creatine combined with strength training does not enhance lower-body strength or bone mineral.

Objectives Insight regarding dietary creatine (Cr) supplementation strategies to acutely increase and maintain muscle total creatine (TCr) content is missing. Methods Healthy, young, men ingested 4 × 5 g Cr/day (d) for 5d, followed by 5 g/d for 28 d (Cr group, n=8). To achieve insulin mediated muscle Cr transport, another group (n=16) ingested 4 × 5 g Cr plus 95 g dextrose/d for 5d (CrCHO), and thereafter two sub-groups ingested 5 g of Cr (CrCHO1, n=8) or 5 g Cr plus 95 g dextrose/d for 28 d (CrCHO2, n=8). A fourth group ingested 4 × 5g of Cr plus 14 g protein, 7 g phenylalanine, 7 g leucine and 57 g dextrose/d for 5 d, and once/d thereafter for 28 d (CrPAC, n=8). Muscle biopsies were obtained at 0, and after 5 and 33 d. Results After 5 d, muscle TCr increased in Cr (p<0.001), CrCHO (p<0.001), and CrPAC (p<0.05) groups, and was numerically greatest in CrCHO; achieving a content reported to be an average maximum (150 mmol/kg). After 33 d, TCr also increased to ~150 mmol/kg in the Cr group (p<0.05), remained unchanged from 5 d in CrCHO2, and tended to decline in CrCHO1. Muscle TCr remained unchanged from 5 d in CrPAC after 33 d, being less than the Cr group (p<0.05). Muscle Cr transporter mRNA expression changed modestly, but the increase in muscle TCr after 5 d was inversely associated with fold-change in mRNA expression (r=0.502, p<0.05). Conclusions A maximum increase in muscle TCr is achieved after 5 d Cr ingestion alongside 95 g dextrose, and continued consumption of Cr with dextrose will maintain this maximum. Ingestion of Cr alone will achieve a high muscle TCr content too, but takes longer.

Objectives Independent mobility (IM), which is defined as the freedom of children moving without adult supervision, has been found to be positively associated with physical activity (PA). This study explored IM by sociodemographic factors and type of neighborhoods and its association with PA among children in Hong Kong. Methods A convenience sample of 330 children aged 8–12 years and their parents was recruited. The children wore an ActiGraph accelerometer for eight consecutive days to measure PA and sedentary time (ST). Parents reported parents’ license and children self-reported their actual mobility. Generalized estimating equations were conducted to examine the associations of IM with sociodemographics (e.g., children’s age, sex, body weight status, parents’ age, sex, maternal education) and type of neighborhood. Linear mixed models were performed to determine the associations of IM with PA and ST. Results Valid data from 296 children (8.8±0.6 years old, 42.2 % boys) were included in analysis. Children residing in sprawl and rural areas had greater parents’ license and actual mobility than those in urban areas. Greater parents’ license was associated with more moderate-to-vigorous intensity PA (MVPA) on weekend days ( β =1.33, 95% CI: 0.15–2.51), while children’s actual mobility was positively associated with MVPA on weekdays ( β =1.14, 95% CI: 0.10–2.18). Conclusions In densely populated metropolis, children living in highly urbanized areas with higher SES experienced reduced parental license and actual mobility compared to their peers in less affluent neighborhoods, irrespective of the level of urbanization.

Objectives Assessing physical activity and cardiometabolic risk in masters athletes as an example of very high physical activity at old age. Methods Forty-three men were studied in full factorial design, either as sprint or jump-trained masters athletes (MA, n=10, age 60–75 years), as young sprint or jump-trained athletes (YA, n=10, age 20–35 years), older control participants (OC, n=11, age 60–75 years) or as young control participants (AC, n=12, age 20–35 years). We performed bio-electrical impedance analysis and assessed serum markers of lipids and glucose metabolism and C-reactive protein, structured training hours, and habitual activity via mobile actimetry. Results Body fat was greater in OC than in MA (23.9 [SD 4.2] % vs. 14.0 [SD 5.7] %, p<0.001), and also greater than in YA and YC (both p<0.001). Weekly training hours were comparable between MA and YA (7.9 [SD3.3] hours vs. 11.1 [SD 4.8] hours, p=0.69). Habitual walking distance was greater in MA than in OC (7,387 [SD 4,923] m/day vs. 4,110 [SD 1,772] m/day, p=0.039), and so was habitual running distance (667 [SD690] m/day vs. 132 [427] m/day, p<0.001). HOMA-index was greater in OC than in MA (2.07 [SD 1.39] vs. 0.80 [SD 0.41], p=0.0039), and so was C-reactive protein (1.35 [SD 1.74] mg/l vs. 0.58 [SD 0.27] mg/ml, p=0.018), whereas serum lipids showed only moderate or no effect (all p between 0.036 and 0.07). Conclusions Improved body composition and physical activity levels in MA are associated with lower cardiometabolic risk, which seems more pronounced for insulin sensitivity and inflammaging than for lipid metabolism.

Objectives To determine how the anti-inflammatory actions of interleukin-10 (IL-10) and IL-6 differ across age and physical activity levels. Methods Using a cross-sectional design, fasted blood samples were obtained from younger physically inactive (YI: n=10, age: 22.7 ± 3.7 years, BMI: 24.8 ± 4.8 kg/m 2 , <150 min of weekly moderate-to-vigorous physical activity [MVPA]), younger highly active (YA: n=11 varsity cross country running athletes, 20.7 ± 2.7 years, 21.1 ± 1.8 kg/m 2 , >300 min of weekly MVPA), and older highly active (OA: 12, 56.0 ± 10.3 years, 22.8 ± 3.2 kg/m 2 , >300 min of weekly MVPA) individuals and analyzed for leukocyte counts, IL-10 and IL-6-related signaling, and cytokine secretion ex vivo. Results Total white blood cells and monocytes were similar between groups (p=0.8) but YA and OA had lower lymphocyte counts than YI (p<0.01). The ability of IL-10 (1 ng/mL) to phosphorylate signal transducer and activator of transcription 3 (STAT3) in CD14 monocytes was greater in YA vs. YI (p<0.03) despite YA having lower IL-10 receptor expression (p<0.01). IL-6 (10 ng/mL) mediated STAT3 phosphorylation in CD4 lymphocytes was higher in OA compared YI (p<0.01), with a similar tendency observed for YA vs. YI (p=0.08). Despite enhanced responsiveness of STAT3 to IL-10/6 in active individuals, the ability of IL-10/6 to inhibit tumor necrosis factor-alpha (TNF-⍺) secretion from lipopolysaccharide-stimulated whole-blood was similar between groups. Conclusions Highly active younger and older individuals demonstrate enhanced IL-10- and IL-6-mediated activation of immune cell STAT3. Although the ability of IL-10/6 to inhibit TNF-⍺ secretion appeared unimpacted by activity level, anti-inflammatory cytokine actions were preserved in older active individuals.

Objectives The purpose was to directly assess in-competition thermoregulatory responses in recreational runners during a city marathon conducted in cool, ambient conditions using a two-pill ingestion strategy. Methods Thirty-two recreational runners (age: 38.7 ± 10.2 years, mass: 73.9 ± 11.0 kg, height: 177 ± 8 cm) were invited to participate in this study. Core temperature was continuously assessed using telemetric ingestible pills. Each runner swallowed two pills: the first pill (Pill 1) 11 h:47 min ± 1 h:01 min pre-race (before overnight sleep) and the second (Pill 2) 2 h:35 min ± 0 h:54 min pre-race (on wakening). Results Pre-race core temperature for Pill 1 was significantly different from Pill 2, with values of 37.4 ± 0.4 °C and 37.1 ± 0.6 °C, respectively (p=0.006). The mean core temperature during the race was higher for Pill 1 compared to Pill 2 (38.5 ± 0.5 °C and 37.8 ± 1.0 °C, respectively; p<0.001). Peak core temperature was higher for Pill 1 compared to Pill 2 (39.1 ± 0.5 °C and 38.8 ± 0.5 °C, respectively; p=0.03). Post-race core temperature was higher for Pill 1 compared to Pill 2 (38.8 ± 0.7 °C and 38.1 ± 1.3 °C, respectively; p=0.02). Conclusions The timing of pill ingestion significantly impacted core temperature and hence timing of pill ingestion should be standardised (5 h:30 min–7 h prior to measurement). Despite the relatively cool ambient conditions during the race, a significant number of runners achieved a high core body temperature (≥39 °C), which was not accompanied by any signs of heat illness.

Objectives To examine the effect of the NAD + precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people. Methods In a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65–75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured. Results Resting and submaximal respiratory exchange ratio was lower (p<0.05) after 2 weeks in the NA group only, but maximal aerobic and anaerobic function and glucose handling were unchanged (p>0.05). Bayesian statistical modelling identified that leak, maximal coupled and maximal uncoupled mitochondrial respiratory states, increased over the 2-week supplemental period in the NA group (probability for a positive change (pd) 85.2, 90.8 and 95.9 %, respectively) but not in PLA. Citrate synthase and protein content of complex II (SDHB) and V (ATP5A) electron transport chain (ETC) components increased over the 2-week period in the NA group only (pd 95.1, 74.5 and 82.3 %, respectively). Mitochondrial and myofibrillar protein synthetic rates remained unchanged in both groups. NA intake altered the muscle transcriptome by increasing the expression of gene pathways related to cell adhesion/cytoskeleton organisation and inflammation/immunity and decreasing pathway expression of ETC and aerobic respiration processes. NAD + -specific pathways (e.g., de novo NAD + biosynthetic processes) and genes (e.g., NADSYN1 ) were uniquely regulated by NA. Conclusions NA might be an effective strategy for improving ageing muscle mitochondrial health.

Objectives Exercise training induces several skeletal muscle adaptations. Beta-guanidinopropionic acid (β-GPA) is a creatine analog that simulates the effect of exercise to induce mitochondrial biogenesis. However, the effects of β-GPA on resistance training adaptation, such as muscle hypertrophy and mitochondrial biogenesis, are unclear. Therefore, using a resistance exercise model in rats, the present study was designed to investigate the effects of β-GPA administration on resistance training adaptations. Methods This study was approved by the Ethics Committee for Animal Experiments at Ritsumeikan University (approval number: BKC2022-009). Male Sprague Dawley rats were randomly divided into placebo or β-GPA groups. β-GPA (1000 mg/kg) was orally administered once daily, starting seven days before the initiation of electromyostimulation as a model for resistance exercise, and continued throughout the training period. Electromyostimulation was applied to the right gastrocnemius muscle via electrical stimulation every other day for a total of 12 sessions Results Peroxisome proliferators-activated receptor-γ co-activator-1α, a regulator of mitochondrial biogenesis, was significantly increased by the combination of training and β-GPA compared to the training leg (p<0.05). Protein expression of Total OXPHOS, a marker of mitochondrial content, was significantly increased by the combination of training and β-GPA compared to the training leg (p<0.05). β-GPA intake reduced muscle mass (main effect of β-GPA, p<0.05) and was associated with muscle protein breakdown-related Fbx32 and LC3-II protein expression levels but did not counteract the increase in muscle mass caused by resistance training. Conclusions Administration of exogenous β-GPA enhanced resistance training-induced mitochondrial biogenesis. Moreover, β-GPA still permitted resistance electromyostimulation-induced muscle mass gains, but that effect was attenuated as compared to placebo.

Multiple Sclerosis (MS) is a chronic neuroinflammatory autoimmune characterized by inflammation-induced lesion formation after immune cell infiltration into the central nervous system. T cells play an intriguing role in MS immunopathology and research over the past decade has shown that tryptophan (TRP)-derived metabolites are crucial molecules affecting T cell differentiation, also in MS, and are modulated by exercise. The aryl hydrocarbon receptor (AHR), for which TRP metabolites are well-known ligands, has been elucidated as main driver of T cell differentiation and an enhanced anti-inflammatory cellular milieu in human MS and preclinical mouse models. By integrating evidence from different research fields, the aim of this article is to summarize and critically discuss the potential of exercise to activate the AHR in T cells by modulating circulating TRP-derived metabolites and to provide a conceptual framework on potential benefits in MS immunopathology.

Objectives The aim of this study was to explore the acute effects of high-intensity interval training (HIIT) on the microvascular circulation and vascular tumor microenvironment (TME) in a patient with uveal melanoma (UM). Additionally, the acceptance of the applied diagnostics and the exercise protocol in a clinical ophthalmic-oncology setting were evaluated. Methods This case-control study included a young adult male patient with UM previously treated with radiation and an age-matched healthy control. Participants underwent a baseline assessment of dynamic retinal vessel analysis (DRVA) and cardiopulmonary exercise testing (CPET) to determine endothelial function and intensity for HIIT. Optical coherences tomography angiography (OCTA) was performed before, immediately and 30 min after one session of HIIT. The primary outcome were changes in ocular vessel parameters and whole body oxygen uptake. Results The UM patient exhibited lower arterial dilation and constriction in the affected eye compared to his healthy eye and both eyes of the healthy control. OCTA revealed heterogeneous patterns of vascular response to HIIT in both participants. The tumor eye showed an increase followed by a significant decrease in vessel density post-exercise, while the healthy control exhibited minor increases. Conclusions The findings of this study highlighted the potential of UM combined with OCTA and DRVA as a model for examine exercise-induced vascular effects within the TME. However, a pre-treated UM as well as detailed image analyses and further research with longitudinal, randomized controlled designs are essential to validate these findings and address methodological limitations. Such investigations could refine integrative cancer treatment.

Objectives Understanding differences between real-world walking speed (RWS) and laboratory-measured walking speed (LWS) is crucial for comprehensive mobility assessments, especially in context of prolonged immobilization. This study aimed to investigate disparities in walking speed following a 60-day bed-rest period. Methods In 11 male participants, RWS was continuously monitored using a tri-axial accelerometer worn on the waist, while LWS was assessed via a 10-m walk test at preferred speed, on three different study days after immobilization. Statistical analyses included Bland–Altman and Pearson’s correlation to evaluate agreement between RWS and LWS, alongside paired-sample t-tests and univariate linear regression models to assess significance of differences and temporal effects on gait speed. Results Results of Bland-Altman analysis showed no agreement between RWS and LWS (mean difference 0.77 m/s) and nonsignificant correlation (r=0.19, p-value=0.3). Paired-sample t-tests indicated significantly lower RWS compared to LWS for all study days (p-value <0.001). Univariate linear regression models demonstrated a significant effect of test day on RWS (p-value <0.001) but not on LWS (p-value=0.23). Conclusions These findings emphasize the importance of integrating both assessments to capture comprehensive mobility changes following prolonged periods of inactivity. Particularly significant is that RWS is constantly lower than LWS, with the former being more representative as it reflects what normally participants would do when not under observation. Lastly, understanding discrepancies between RWS and LWS would allow for more appropriate rehabilitation programs to speed up recovery while simultaneously keeping the rehabilitation safe and tailored.

Purpose To determine the association between lower-body strength and lower-body power capacities with sprint swimming performance in adolescent competitive swimmers. Methods A total of 44 front crawl swimmers (27 males and 17 females) performed anthropometric assessments, lower-body strength tests (half squat maximum isometric strength, dynamic half squat with 20, 30 and 40 % of the maximum isometric strength, and knee extension maximum isometric strength) and lower-body power tests (squat jump [SJ], countermovement jump [CMJ] and Abalakov jump). Further front crawl swimming best times in 50 and 100 m were recorded from official swimming competitions and front crawl technique was assessed by an experienced coach using a visual analogue scale. Results Swimming performance was correlated with lower-body power variables (SJ [r=−0.573 for 50 m and −0.642 for 100 m], CMJ [r=−0.497 for 50 m and −0.544 for 100 m], and Abalakov jump [r=−0.452 for 50 m and −0.415 for 100 m]; p≤0.05) and lower-body strength (half squat maximum isometric strength [r=−0.430 for 50 m and −0.443 for 100 m]; p≤0.05) in males but not in females. Further linear regression models showed that only lower-body power predicted both 50 m (Abalakov jump; r 2 =0.58; change in r 2 =0.18) and 100 m (SJ; r 2 =0.66; change in r 2 =0.15) performance in male swimmers. Conclusions This study emphasizes the greater association between lower-body power and sprint front crawl performance in adolescent males compared to females. Practical tests (i.e., SJ and Abalakov jump) are shown to predict front crawl swimming performance, which may facilitate the performance control by coaches and trainers.