Parkinson's disease (PD) is the second most common neurodegenerative disease that affects movement and cognitive function, resulting from the loss of the neurotransmitter dopamine due to the death of dopaminergic neurons. It affects nearly one million people in the United States and 8.5 million worldwide. While there are some pharmacological and surgical options available, they only provide symptomatic relief, as there is currently no cure for PD. In contrast, exercise training, a non-pharmacological intervention, has emerged as a powerful strategy to enhance the psychological, cognitive, and physiological (motor) impairments associated with PD. Given that the beneficial effects of exercise differ based on the intensity and type of training, gaining a thorough understanding of the molecular mechanisms underlying exercise-induced protection is crucial for developing innovative therapies that improve the quality of life for PD patients around the globe. This review discusses PD pathogenesis and pathophysiology and provides recent clinical evidence of neuroprotective benefits from various exercise modalities and intensity. Furthermore, the molecular mechanisms of exercise in PD pathogenesis (e.g., modulations on neurotrophic factors, oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, and autophagy) will be emphasized.
Aging is characterized by a progressive decline in physiological function, driven by intrinsic mechanisms (primary aging) and modifiable factors (secondary aging), ultimately leading to multimorbidity, disability, and mortality. Mitochondrial dysfunction, a major hallmark of aging, plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia. With age, mitochondrial quality control processes, including biogenesis, mitophagy, and dynamics, become dysregulated, impairing energy metabolism and muscle homeostasis.
Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty, such as the decrease in walking speed and muscle strength, making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity. Mitohormetic agents induce reversible mitochondrial stress, triggering adaptive responses that enhance function. Among these interventions, physical exercise, particularly endurance and resistance training (RT), has been reported to be among the most effective, as it may modulate mitochondrial biogenesis, dynamics, and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) expression, mitochondrial deoxyribonucleic acid (mtDNA) copy number, and mitochondrial content. Chronic RT can also elevate fusion and fission markers, potentially as a compensatory mechanism to mitigate mitochondrial damage.
Apart from exercise, mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field. By modulating mitochondrial bioenergetics and dynamics, they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.
Background: This paper aimed to systematically review the literature regarding the effects of resistance training (RT) performed at longer-muscle length (LML) versus shorter-muscle length (SML) on proxy measurements for longitudinal hypertrophy.
Methods: We included studies that satisfied the following criteria: (1) be a resistance training intervention with a comparison of LML vs SML-RT; (2) assess both fascicle length (FL) and muscle size pre- and post-intervention; (3) involve healthy adults aged ≥ 18 years; (4) be published in an English-language journal, and; (5) have a minimum training intervention duration of 4 weeks. Three databases were searched in February 2024 (Google Scholar, PubMed/Medline, Scopus) for relevant articles, alongside 'forward' and 'backward' citation searching of articles included and additions via authors' personal knowledge. The results of studies were described narratively, compared, and contrasted. Eight studies met the inclusion criteria, totaling a sample size of 120.
Results: Our results suggest that both muscle size and fascicle length increases may be greater following LML-RT versus SML-RT, suggesting LML-RT may lead to greater longitudinal hypertrophy than SML-RT. Notably, evidence is largely mixed; no studies to date have attempted to estimate serial sarcomere number changes from LML versus SML-RT, and all but one study used linear extrapolation methods to estimate FL, which has questionable validity. Therefore, the structural adaptations underlying hypertrophy from LML-RT remain undetermined.
Conclusion: In conclusion, results suggest that LML-RT may be superior to SML-RT for inducing muscle hypertrophy and, more specifically, longitudinal growth, though evidence is mixed.
Background: The topic of this review is the study of the gut microbiota (GM), and the use of probiotics, especially in humans, as a new frontier in the field of prevention and health in general. The beneficial effects and functions performed by probiotics in the GM are increasingly at the centre of both scientific, medical, and pharmaceutical interest. It is now known that diet and probiotics can modify the GM, although in these situations there is a need for greater and more in-depth research regarding the methods and timing of treatment. However, the relationship between physical activity, GM, and probiotics is still largely unclear, as regards certain mechanisms between physical exercise and probiotics in humans.
Discussion: In this study, we tried to demonstrate whether and how physical exercise was able to alter the composition of the microbiota and how probiotics can facilitate it. Therefore, alteration of the microbiota was considered in terms of both diversity and composition.
Conclusions: The ones examined propose vastly different physical exercises, both in terms of timing and type of intervention itself, and the use of probiotics.
Resistance exercise has been confirmed to be important for maintaining muscle mass and function. However, despite considerable experimental studies, the underlying mechanisms still requires further investigation to be elucidated. Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction. Besides, oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy, whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress. Nevertheless, whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown. Here we show that six-week resistance exercise training significantly improved muscle function, muscle mass, and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice. Mechanistically, Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes. Furthermore, an emerging regulator of cellular defense against toxic and oxidative insults, nuclear factor erythroid2-related factor 2 (Nrf2) controls the basal and induced expression of an array of antioxidant response element-dependent genes to regulate the pathophysiological outcomes of oxidant exposure. In this study, we found that Nrf2 is a target of Sestrin1, and Nrf2 nuclear translocation is facilitated by Sestrin1. ML385 (an Nrf2 inhibitor) treatment mitigated the regulatory effects of overexpression-Sestrin1. Therefore, Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy, which may be closely related to its antioxidant capacity, revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
This study aims to explore the impact of fatigue induced by different limb exercises on cerebral cortical oxygenation levels and functional connectivity strength using functional near-infrared spectroscopy (fNIRS). Fatigue was induced using an upper limb ergometer or a lower limb ergometer, with the load increasing gradually each minute. fNIRS covering the prefrontal cortex and motor cortex were used to collect data during the resting state, both before and after fatigue induction. A two-way ANOVA was conducted to examine differences in oxyhemoglobin (HbO2) and functional connectivity before and after fatigue induction in both groups, with the significance level set at 0.05. Exercise-induced fatigue in both the upper and lower limbs leads to a significant decrease in cerebral cortical oxygenation levels. Upper limb fatigue leads to a significant reduction in functional connectivity, there were significant decreases in connectivity within the motor cortex, between the motor cortex and frontal regions, and between the right ventrolateral prefrontal cortex and other frontal regions. Conversely, no significant changes were observed before and after lower limb fatigue. Future studies should focus on examining the extent to which how changes in the cerebral cortex, induced by exercise fatigue, are linked to exercise- and/or performance-related outcomes.
Background: Cupping therapy (CT), an ancient practice revived in modern sports medicine, offers potential benefits for athlete recovery and performance. Distinctions between wet CT (WCT) and dry CT (DCT) in sports science focus on their effects on recovery metrics, particularly how they influence sleep quality, perceived wellness, and athletic performance. Despite anecdotal evidence of its efficacy, rigorous comparative studies are scarce.
Objective: This study aimed to evaluates and compare the effects of WCT and DCT on endurance, perceived wellness, exertion levels, and sleep quality among young, active males, addressing the gap in the literature regarding CT's efficacy in sports performance and recovery.
Methods: Thirty- two amateur runners were randomly divided into two groups: one followed WCT sessions and the other followed DCT sessions. The study assessed the interventions' impacts on endurance performance (Yo-Yo intermittent recovery test), sleep quality (Pittsburgh Sleep Quality Index), and perceived exertion (Borg CR10 Scale). Heart rate was measured using a Polar H10 sensor to gauge physiological responses during physical tests.
Results: Significant improvements were observed in the WCT group for sleep latency (% change = −82.31%; interaction group × time p = 0.006; Cohen's d = 0.74) and sleep disturbance (% change = −68.70%; interaction group × time p < 0.001; Cohen's d = 1.09), suggesting enhanced sleep quality (global score; % change = −52.81; interaction group × time p = 0.004; Cohen's d = 0.77). However, no significant differences were found in direct performance metrics (distance, maximal heart rate, maximal oxygen uptake) between WCT and DCT groups. These findings highlight WCT's potential as a recovery aid, particularly through improved sleep, without directly influencing endurance performance outcomes.
Conclusion: WCT may serve as an effective ergogenic aid for athletes by potentially improving sleep quality and reducing perceived exertion, thus contributing indirectly to performance through enhanced recovery.
Purpose: ATLAS is a cross-sectional study aiming to investigate environmental and genetic determinants of athletic performance in healthy Greek competitive athletes (CA). This article presents the study design, investigates the muscle strength performance (MSP) of 289 adult and teenage CA, exercisers, and physically inactive individuals (PI), and proposes predictive models of MSP for adults.
Methods: Muscle maximal, speed, and explosive strength (MMS/MSS/MES) at unilateral maximal concentric flexion and extension contraction (FC/EC) were evaluated using Biodex System 3 PRO™ at 60 °/s, 180 °/s, and 300 °/s, while additional performance markers were assessed through field ergometric testing. Participants were interviewed about their lifestyle, dietary habits, physical activity, injury, and medical history. Body composition was assessed via bioelectrical impedance. gDNA was extracted from biochemical samples and then genotyped. Statistical analysis was conducted using IBM SPSS Statistics v21.0 and R.
Results: Age, fitness, and sex impacted correlations of MSP with body composition and anthropometric measurements (p < 0.05). Among CA, females outperformed males in accuracy (p < 0.001) while, males outperformed females in anaerobic power, MSP, speed, and endurance (p < 0.001). Adult CA outperformed exercisers and PI in MMS, MSS, and MES (p < 0.05). Multiple linear regression models, with predictors age, FFM, body extremity, training load explained the majority of variation in MMS (R2adj:71.4%-88.9%), MSS (R2adj:64.8%-78.4 %), and MES (R2adj:52.7%-68.4 %) at EC, FC, and their mean (p < 0.001).
Conclusions: Muscle-strengthening strategies should be customized according to individual fitness levels, body composition, and anthropometric measurements. The innovative sex-specific regression models assessing MMS, MSS, and MES at EC and FC provide a framework for personalizing rehabilitation and skill-specific training strategies.
Purpose: Ankle proprioception deficits have been widely reported in patients with chronic ankle instability (CAI), but their central neuropathological mechanisms have not been fully discussed. So, we aimed to figure out whether the structural and functional features of the cerebellar vermis differed between patients with CAI and healthy controls, and are associated with proprioception deficits in patients.
Methods: Twenty- two patients and 25 control individuals were enrolled in a cross-sectional investigation. All participants underwent structural and resting-state functional magnetic resonance imaging scanning to calculate voxel-based morphometry (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) of the vermis. Between-group comparisons of the ankle instability-related subregions of the vermis were performed. Correlation analyses were performed between the outcomes of the surviving subregions and the proprioceptive scores of the ankle inversion discrimination apparatus for landing test.
Results: The subregion of vermis IV/V survived the multiple comparison correction to reveal a lower VBM value in patients than in healthy controls (Cohen's d = −0.968). The patients also showed significantly higher fALFF (Cohen's d = 0.666) in this subregion. After controlling the demographic features, the proprioceptive scores were significantly correlated with VBM (r = 0.622) and fALFF values (r = −0.512) in the group of patients.
Conclusions: Patients with CAI have lower gray matter volume and higher activity intensity in the cerebellar vermis than healthy control. The more severe proprioception deficits were significantly associated with the vermal volume and activity, which might be able to facilitate future diagnoses and treatments for CAI.
Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia (EIH). Transcranial direct current stimulation (tDCS), acting on similar analgesic mechanisms as EIH, represents a potential complementary intervention that may amplify the effects of exercise on pain. This study aimed to explore if anodal tDCS could enhance the effect of exercise on pain compared to exercise alone. A total of 35 healthy participants aged 19-37 years completed a familiarisation session followed by two separate sessions where active and sham tDCS was applied in a randomised cross-over design. The familiarisation session involved familiarisation to the pain assessment and exercise tasks, while the subsequent tDCS sessions involved pain sensitivity assessment, exercise and either anodal tDCS or sham tDCS. tDCS doses were applied at 2 mA over the primary motor cortex for 10 min, with the reference electrode placed over the contralateral supraorbital area. The exercise task involved a sustained isometric grip strength contraction at 35% of maximal voluntary contraction (MVC) until volitional exhaustion. Pain sensitivity was evaluated as pressure pain threshold before tDCS, after tDCS, and after exercise. Across both tDCS conditions, pain threshold was higher after exercise when compared to pre- and post-tDCS measurement. This increase in pain threshold did not differ between active and sham tDCS conditions. Our findings suggest that the hypoalgesic effects of active anodal tDCS over the motor cortex prior to exercise are no greater than the effects of sham tDCS prior to exercise.
Background: Exercise exerts tumor-suppressive effects across multiple malignancies, partly through exerkines—exercise-induced secreted factors with immunomodulatory and metabolic functions. However, the prognostic relevance of exerkines across cancer types remains unclear, and the molecular determinants of exercise responsiveness are poorly defined.
Methods: We systematically profiled 183 curated exerkine-related genes across 33 cancer types from The Cancer Genome Atlas (TCGA) using non-negative matrix factorization (NMF) to define molecular subtypes. Prognostic significance was evaluated via Kaplan-Meier analysis. For five cancers with consistent survival divergence (LGG, KIRC, LUAD, PAAD, ACC), we developed an Exerkine Prognostic Index (EPI) using LASSO Cox regression and validated its predictive performance through time-dependent ROC analysis. Immune cell infiltration (CIBERSORT), stromal/immune scores (ESTIMATE), and immune checkpoint expression were assessed to characterize immune landscape differences between EPI subgroups.
Results: Exerkine- based NMF clustering identified prognostically distinct subtypes in 25 cancers. The EPI robustly stratified patients into high- and low-risk groups with significant differences in overall survival (p < 0.001). High-EPI subgroups were associated with elevated infiltration of immunosuppressive cells (e.g., Tregs, M0 macrophages), altered immune/stromal scores, and differential expression of immune checkpoints such as PD-L1 and CTLA4 in a cancer-type-specific manner.
Discussion: Our findings reveal that exerkine expression patterns capture biologically and clinically relevant heterogeneity across cancers. The EPI provides a robust molecular tool to stratify patients by prognosis and immune contexture, offering insights into differential exercise responsiveness.
Conclusions: Exerkines represent promising biomarkers for risk stratification and precision-guided exercise interventions in oncology.