Purpose: This study investigated whether the combined application of treadmill exercise and vitamin D injections exerts neuroprotective effects in nonpathological mice by enhancing cognitive function, regulating immune responses, preserving blood-brain barrier (BBB) integrity, and improving mitochondrial efficiency.Methods: Forty male C57BL/6 mice were randomly assigned to control, exercise (EX), vitamin D (VD), or combined treatment (EXVD) groups. After 20 weeks of intervention, behavioral, molecular, and cellular analyses were performed to assess cognitive function, immune responses, BBB integrity, oxidative stress, and mitochondrial efficiency.Results: The EXVD group demonstrated superior spatial learning and memory compared to the other groups. Vitamin D treatment significantly increased plasma interleukin-10 and tight junction protein levels, while exercise alone elevated hippocampal tumor necrosis factor-α. Combined treatment reduced astrocyte activation, maintained BBB integrity, and improved mitochondrial respiratory efficiency without increasing oxidative stress. Expression of antioxidant enzymes was decreased in the VD and EXVD groups, indicating improved redox balance.Conclusions: Treadmill exercise and vitamin D injections confer neuroprotective effects in nonpathological mice by enhancing cognition, reducing neuroinflammation, and improving both BBB integrity and mitochondrial function. These findings highlight the potential of nonpharmacological strategies to support brain health even in the absence of disease.

Background: Estrogen deficiency following human menopause or rodent ovariectomy (OVX) induces adverse alterations in body composition and metabolic function. This study investigated the combined effects of acetic acid supplementation and voluntary exercise on metabolic health and skeletal muscle mitochondrial function using an OVX mouse model. Methods: Forty female C57BL/6J mice (8 weeks old) were randomly assigned to 5 groups: sham (SHM), ovariectomized control (OVX), OVX with exercise (OVX-E), OVX with acetic acid (OVX-A), and OVX with both interventions (OVX-AE). Following a 1-week recovery from OVX, a 13-week intervention was initiated: 5% sodium acetate-supplemented chow and/or voluntary wheel running. Body composition, glucose tolerance, total energy expenditure, skeletal muscle mitochondrial function, and the contents of AMPKα, PGC-1α, and carbonyl protein were assessed. Results: OVX impaired whole-body metabolism and skeletal muscle mitochondrial function, specifically in the gastrocnemius muscle. While the exercise alone failed to mitigate the OVX-induced mitochondrial dysfunction, the combined treatment of exercise and acetic acid supplementation significantly rescued from the OVX-induced mitochondrial dysfunction. Conclusions: OVX resulted in detrimental changes in whole-body metabolism, but voluntary exercise and/or acetic acid supplementation had no rescuing effects on those parameters. In gastrocnemius muscle, acetic acid supplementation during exercise enhanced mitochondrial function in OVX mice.

PURPOSE: This study examined the effects of different types of exercise on bone metabolism and bone mineral density (BMD) in elderly individuals. Additionally, we sought to comprehensively analyze the physiological mechanisms underlying the prevention and management of osteoporosis through exercise.METHODS: This review included previous publications found in PubMed, Google Scholar, and Science Direct databases.RESULTS: Aerobic exercise was found to stimulate osteoblast activity and enhance bone formation by activating the Wnt/β-catenin signaling pathway, suppressing sclerostin expression, reducing pro-inflammatory cytokines, and promoting vitamin D metabolism. In contrast, resistance exercise increased the expression of genes associated with osteoblast differentiation and bone formation by applying a mechanical load to the bone, while simultaneously inhibiting osteoclast-related markers, thereby reducing bone resorption. Moderateintensity exercise showed the most significant improvements in bone metabolism across both types of exercise.CONCLUSIONS: Both aerobic and resistance exercises are effective non-pharmacological interventions for maintaining bone health and preventing osteoporosis in elderly individuals. Combined exercise, incorporating both types of exercise, appears to be more effective in optimizing the balance between bone formation and resorption, leading to improved BMD. In conclusion, aerobic and resistance exercises serve as beneficial nonpharmacological strategies for enhancing bone microarchitecture, maintaining BMD, and improving bone metabolism, thereby contributing positively to bone health in the elderly population.

PURPOSE: This study aimed to investigate the mediating role of physical activity in the association between oral health and depression among Korean individuals aged ≥65 years.METHODS: Data were obtained from the 2023 Korea Community Health Survey, comprising 68,806 participants aged ≥65 years. Oral health was assessed using two self-reported indicators: perceived oral health status and chewing discomfort. According to the revised edition of the Physical Activity Guidelines for Koreans, physical activity was categorized into three levels (inactive, insufficient, and sufficient). Depression was defined as a score of 10 or higher on the Patient Health Questionnaire-9. The mediating effect of physical activity on the relationship between oral health and depression was analyzed using the PROCESS macro (Model 4).RESULTS: Poorer oral health was significantly associated with a higher level of depression (path a, β=-0.019, p<.001), while higher levels of physical activity were inversely associated with depression (path b, β=-0.083, p<.001). Furthermore, physical activity partially mediates the relationship between oral health and depression (indirect effect, β=0.002, 95% CI=0.001 to 0.002), accounting for approximately 0.6% of the total effect.CONCLUSIONS: These findings indicate that engaging in regular physical activity may partially reduce the risk of depression resulting from deteriorating oral health, suggesting its potential as a complementary strategy for the prevention and management of depression associated with declining oral health.

PURPOSE: This study aimed to investigate the association among liver fibrosis, physical activity, and bone mineral density in Korean adults.METHODS: Data from 8,019 participants aged 40–69 years in the 2008–2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Bone mineral density was measured using dual-energy X-ray bone densitometry (DXA). Liver fibrosis was defined using the fibrosis-4 (FIB-4) index. Physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ). Logistic regression analysis was used to examine the associations among liver fibrosis, physical activity, and osteoporosis.RESULTS: Participants with liver fibrosis had a significantly higher risk of osteoporosis (OR=1.857, 95% CI=1.682-2.051, p<.001) compared to those without fibrosis. Similarly, physically inactive participants had a higher risk of osteoporosis (OR=1.392, 95% CI=1.273-1.523, p<.001) than physically active participants. After adjusting for age and sex, compared to the normal/active group (reference=1), the normal/inactive (OR=1.299, 95% CI=1.155-1.461, p<.001) and fibrosis/inactive groups (OR=1.243, 95% CI=1.058-1.461, p=.008) had a significantly higher risk of osteoporosis. Furthermore, after further adjustment for education, marital status, region, income, smoking, and chronic diseases, the association remained significant in the normal/inactive group (OR=1.279, 95% CI=1.137-1.439, p<.001) and fibrosis/inactive group (OR=1.216, 95% CI=1.033-1.431, p=.019). However, after further adjustment for body mass index, the association remained significant in the normal/inactive group (OR=1.213, 95% CI=1.074-1.370, p=.002).CONCLUSIONS: Our results suggest that physical activity is associated with the attenuation of the risk of osteoporosis associated with liver fibrosis. However, further studies are required to determine the relationship between other covariates and osteoporosis.

Purpose: Aging is associated with a progressive decline in skeletal muscle function and motor coordination, contributing to reduced mobility and quality of life. While exercise is a well-established intervention to counteract age-related deterioration, the underlying molecular mechanisms in both muscle and the brain remain incompletely understood.Methods: Young (4 months) and aged (20 months) male C57BL/6N mice were assigned to control or treadmill exercise groups. After 8 weeks of training, the grip strength, muscle histology, rotarod performance, and molecular markers related to muscle hypertrophy and brain plasticity were analyzed.Results: Treadmill exercise significantly increased grip strength in both young and aged mice without changes in muscle fiber size, indicating improved muscle quality. Molecular analysis revealed upregulation of insulin-like growth factor 1/AKT/mammalian target of rapamycin (mTOR) and mTOR/p70 ribosomal protein S6 kinase signaling in both young and aged mice. Exercise also modulated myogenic markers in an age-dependent manner, increasing paired box 3 (Pax3) and myogenic differentiation 1 in aged mice and Pax7 in young mice. Rotarod performance significantly improved over time, suggesting enhanced motor coordination and learning. These functional gains were accompanied by elevated hippocampal brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression.Conclusions: Eight weeks of treadmill exercise enhances muscle strength and motor performance in both young and aged mice. These benefits occur independently of muscle hypertrophy and are associated with favorable molecular adaptations in muscle and the brain. These findings underscore the potential of exercise to preserve neuromuscular function during aging through peripheral and central mechanisms.