Journal of Exercise & Organ Cross Talk

Abstract The global increase in the older population has resulted in escalating healthcare costs and burdens on governments and families. Understanding biological age (BA) as distinct from chronological age (CA) holds significant potential in accurately assessing individuals' health status and susceptibility to diseases. During exercise, myokines like irisin and lactate are released from skeletal muscles, facilitating cross-talk with organs such as the brain and heart. This may improve physical fitness, reducing frailty and BA. This research aimed to develop a comprehensive BA prediction model integrating genetic and epigenetic factors. The study involved 59 healthy adults, comprising 31 males and 28 females, with average ages of 58.2 ± 7 years and 50.1 ± 8.5 years, respectively. Assessments of physical fitness and completion of the Frailty Index (FI34) questionnaire were conducted to capture genetic and epigenetic influences. Feature selection, principal component analysis (PCA), and multiple linear regression (MLR) were employed to tailor BA prediction models for each gender. We identified seven significant biomarkers for males, including FI34, percent of skeletal muscle mass (SM), handgrip strength (GS), flexibility via sit-and-reach test (SR), peak torque of quadriceps muscles (PTQ), cardiopulmonary fitness (VO₂max), and basal metabolic rate (BMR). Conversely, females exhibited six key biomarkers: FI34, SM, GS, waist-to-hip ratio (WHR), peak torque of hamstring muscles (PTH), and percentage of body fat (PBF). We have successfully developed a comprehensive model for estimating BA by integrating key biomarkers representing epigenetic and genetic impacts. Estimating BA is crucial for precise health evaluations and disease risk assessments.

Abstract The aim of this study was the effect of endurance exercise and probiotic supplement enriched with amino acid leucine and vitamin D on the gut-muscle axis in aged male rats. For this purpose, 25 male Wistar rats (5 rats in each group) in two age groups of 8 to 12 weeks (young) and 18 to 24 months (elderly) were randomly divided into 5 equal groups of old control (OC), young control (YC), endurance exercise (OE), supplement group (OS) and endurance exercise plus supplement (OES) were divided. The results showed that 8 weeks of endurance training (three times a week) and supplemental oral gavage (5 times a week) caused a significant change in postbiotics (decrease of indoxyl sulfate (IXS) and increase of Short-chain fatty acids (SCFAs)). The role of OS in reducing IXS was more prominent than OE and OES variables; of course, the synergistic effect of OES (P=0.000), caused a greater improvement in the amount of SCFA. Also, Administering the supplement alone and at rest (without exercise) could not cause a significant increase in VO_2max (P=0.449). But, the effect of exercise on increasing VO_2max index was more effective than OS and even OES. Eventually, the independent variables made a significant difference on the Villus height (VH) (except for the OS group) and number of goblet cells (GC) compared to the OC group (P<0.05).

Abstract Unmanaged Type 2 Diabetes (DM2) is a known risk factor for cognitive decline, dementia, and Alzheimer's disease (DM3). This study explores the combined effects of high-intensity interval training (HIIT) and thyme honey on the expression of genes involved in memory-related signaling pathways (BDNF-TrkB-CREB), which are compromised in both DM2 and DM3. This experimental study involved 36 young male Wistar rats, divided into four groups: control (C), HIIT (T), thyme honey (H), and HIIT-thyme honey (TH). The T and TH groups underwent 40 training sessions over two months, with progressively increasing intervals (from 2 to 8) and intensity (from 80% to 95% of maximum running speed). Concurrently, the H and TH groups were administered 3 g/kg of thyme honey 5 days a week. Changes in BDNF, TrkB, and CREB gene expression were assessed using RT-PCR. The data were analyzed through one-way ANOVA, Bonferroni post hoc test, and Univariate analysis using SPSS-22 software. A significant increase in BDNF and CREB expression in the interactive intervention group and the expression of the TrkB gene in honey intervention groups were observed compared to diabetic control (P≥0.001). The interactive intervention with HIIT exercises and thyme honey has a synergistic effect on increasing gene expression in memory-related pathways. The highest effect size was observed for HIIT training on BDNF (EF=0.667) and CREB (EF=0.540), while the honey intervention showed a significant effect size on TrkB (EF=0.666).

Abstract Recent studies highlight the role of molecular pathways, such as oxidative stress response and mitochondrial function, in COPD. This study explores the role of the PGC-1α gene, a key regulator of mitochondrial biogenesis and energy metabolism, using a rat model and bioinformatics analysis of human lung tissue samples. This study utilized a combined approach, analyzing gene expression in rat lung tissue alongside bioinformatics analysis of public human datasets. A total of 42 male Wistar rats were divided into seven groups, receiving treatments including cigarette smoke extract (CSE), nano-selenium (SeNPs), and aerobic interval training (AIT). PGC-1α expression levels were evaluated using quantitative Real-Time PCR (qRT-PCR) and analyzed using one-way ANOVA, followed by Dunnett’s post hoc test for multiple comparisons to determine significance across groups. The CSE+SeNPs+AIT group exhibited significantly higher PGC-1α expression compared to controls (p = 0.0289), indicating a potential protective role of SeNPs and exercise against oxidative stress. Bioinformatics analysis identified 250 differentially expressed genes (DEGs), with PGC-1α emerging as a critical hub gene associated with pathways like oxidative stress response and mitochondrial regulation. Protein-protein interaction (PPI) analysis further highlighted the centrality of PGC-1α in COPD pathophysiology. This study underscores the importance of PGC-1α in regulating mitochondrial function and oxidative stress in COPD. The findings suggest that PGC-1α could serve as a potential therapeutic target, offering insights into the development of interventions aimed at improving respiratory health in COPD patients. Future research should focus on validating these findings in clinical settings and exploring the therapeutic potential of PGC-1α modulation.

Abstract Resistance exercises and nutritional strategy are the best ways to prevent with age- related muscle atrophy (sarcopenia) by improving the physiological function of skeletal muscle. This study investigated the effect of 8 weeks of Water resistance training with consumption of dark chocolate on the changes and correlation of IGF-1 and FOXO3 in elderly women. In this study, 40 sedentary elderly women with an age range of 60-73 years were randomly divided into four groups: 1. water resistance training, 2. water resistance training + dark chocolate, 3. dark chocolate, 4. control. The subjects of the training groups did water resistance training for eight weeks. During these 8 weeks, the dark chocolate groups consumed 30 grams of 83% dark chocolate every day, and the control group received neither exercise nor Dark chocolate. Blood sampling was done 48 hours before the study and after the end of the last training session. Expressions of IGF-1 and FOXO3 were measured by real time-PCR method. After 8 weeks of water resistance training and consumption of dark chocolate, the expression of insulin-like growth factor 1 (IGF-1) gene increased significantly compared to the pretest (p<0.05). However, FOXO3 did not change significantly (p>0.05). These findings underscore the potential of targeted exercise and dietary interventions in enhancing muscle health among the elderly, although further research is needed to understand the implications of unchanged FOXO3 in this context.

Abstract Cancer is now the leading global cause of death, with breast cancer being particularly deadly for women. This study investigates how physical activity combined with anti-PD-L1 antibody administration affects tumor weight and lifespan in mice with breast cancer. In this study, 30 male and female BALB/c mice, averaging 17.76 grams in weight, were selected and divided into the following groups: PCG (n=6), EIC (n=6), EIE (n=6), EIA (n=6), and EIE+A (n=6). Following an acclimation period on the treadmill, mice underwent two initial 4-week training protocols, followed by a 2-week protocol after cancer induction. A one-way analysis of variance (ANOVA) was performed to analyze the research variables. Statistical analysis showed no significant changes in survival time or tumor weight in the PCG, EIC, and EIE groups of breast cancer mice. However, the EIA and EIE+A groups demonstrated significant improvements in both survival and tumor weight reduction (p<0.05). The findings of this study suggest that the combination of physical activity and anti-PDL-1 antibody administration may lead to tumor apoptosis by enhancing positive immunological effects, which could be effective for better cancer management. However, it is recommended that future studies investigate the immunological and physiological effects of the tumor microenvironment with the combination of physical activity and anti-PDL-1 antibody administration.

Abstract Most of the intracellular and extracellular factors that play a vital role in regulating energy metabolism and determining cell fate converge in the mitochondria. To promote or hinder cell survival through regulating the function and maintaining the mitochondrial structure. The decline of mitochondrial function and homeostasis with aging is the basis of the pathogenesis of aging-related diseases, especially in skeletal muscles. One of the important components of mitochondrial quality control that helps maintain the homeostasis of myocytes is autophagy, which is an important biological and evolutionary process, and its vital function is the removal of defective organelles. Although it has been proven that regular sports activities act as autophagy stimulators and play a role in maintaining the cellular homeostasis of skeletal muscle fibers and regulating intracellular metabolism. However, cellular autophagic responses to exercise in skeletal muscle appear to be different in different exercise protocols and disease models. How exercise activity modulates autophagy in skeletal muscle and how the effect of exercise is regulated by the autophagy signaling pathway are still poorly understood. The importance of understanding the obscure angles of this process can be an important goal in preventing the pathology of age-related diseases in skeletal muscle.

Abstract This article explores the impact of exercise training on brain health in older adults, focusing on the concept of muscle-brain crosstalk. As the global population ages, understanding how lifestyle interventions like exercise can support cognitive function is increasingly important. The article reviews evidence suggesting that physical activity, particularly aerobic and resistance training, plays a crucial role in maintaining and enhancing brain health. It discusses the mechanisms underlying the beneficial effects of exercise, including improved blood flow, neurogenesis, and the release of myokines proteins produced by muscle contractions that influence brain function. Additionally, the article highlights how these myokines facilitate communication between muscles and the brain, contributing to neuroplasticity, reduced inflammation, and enhanced cognitive abilities. The concept of muscle-brain crosstalk is emphasized as a key factor in understanding how exercise promotes brain health, with potential implications for designing targeted interventions to preserve cognitive function in older adults. The article concludes by suggesting that regular exercise should be a cornerstone of public health strategies aimed at improving the quality of life and cognitive health in aging populations. Further research is encouraged to deepen our understanding of the molecular pathways involved and to develop personalized exercise programs that maximize brain health benefits for older adults.