Search Results (11)

According to the World Health Organization (WHO), a healthy lifestyle is defined as a way of living that lowers the risk of becoming seriously ill or dying prematurely. Physical activity, as a well-known contributor to overall health, plays a vital role in supporting such a lifestyle. Exercise induces complex molecular responses that mediate both acute metabolic stress and long-term physiological adaptations. FGF21 (fibroblast growth factor 21) and GDF15 (growth differentiation factor 15) are recognized as metabolic stress markers, while their receptors play critical roles in cellular signaling. However, the differential gene expression patterns of these molecules in trained and untrained individuals following exhaustive exercise remain poorly understood. This study aimed to examine the transcriptional and protein-level responses in trained and untrained individuals performed a treadmill maximal exercise test to voluntary exhaustion. Blood samples were collected at six time points (pre-exercise, immediately post-exercise, and 0.5 h, 6 h, 24 h, and 48 h post-exercise). Gene expression of FGF21, GDF15, FGFR1 (fibroblast growth factor receptors), FGFR3, FGFR4, KLB (β-klotho), and GFRAL (glial cell line-derived neurotrophic factor receptor alpha-like) was analyzed using RT-qPCR, while plasma protein levels of FGF21 and GDF15 were quantified via ELISA. The results obtained were statistically analyzed by using Shapiro–Wilk, Mann–Whitney U, and Wilcoxon tests in Statistica 13 software. Untrained individuals demonstrated significant post-exercise upregulation of FGFR3, FGFR4, KLB, and GFRAL. FGF21 and GDF15 protein levels were consistently lower in trained individuals (p < 0.01), with no significant correlations between gene and protein expression. Trained individuals showed more stable expression of genes, while untrained individuals exhibited transient upregulation of genes after exercise. Full article

Background: Our previous research in an experimental model of current environmental human exposure to cadmium (Cd) (female rats fed a diet containing Cd at 1 and 5 mg/kg for up to 2 years) revealed that chronic treatment with this toxic element destroyed the metabolism of the bone tissue, decreased mineralisation, and weakened bone biomechanical properties, whereas the co-administration of a 0.1% chokeberry (Aronia melanocarpa L. (Michx.) Elliott berry) extract (AME) ameliorated the osteotoxic action of Cd. Methods: In this study, it was explored whether the unfavourable effect of Cd and the protective action of AME might be mediated by the impact on the metabolism of bone essential elements such as calcium (Ca) and inorganic phosphorus (P_i), including the pathways of its regulation by calciotropic hormones (parathormone—PTH, calcitonin—CT, and 1,25-dihydroxyvitamin D₃—1,25(OH)₂D₃) and Klotho. Results: Low-level Cd treatment (1 mg/kg) caused only a temporary elevation in the serum PTH concentration and a decline in the concentration of CT. Moderate treatment with Cd (5 mg/kg) destroyed the body homeostasis of both mineral elements (lowered their concentrations in the serum and enhanced urinary loss), influenced the serum concentrations of Klotho and calciotropic hormones, as well as reduced the concentrations of 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-OHase) and 1,25(OH)₂D₃ in the kidney. The application of AME during Cd intoxication improved the pathways involved in maintaining Ca and P_i homeostasis and allowed subjects to maintain the proper levels of these elements in the serum and urine. Conclusions: In conclusion, Cd at low-to-moderate exposure may exert an unfavourable impact on bone by influencing the pathways involved in regulating Ca and P_i metabolism and destroying the body status of these minerals. It seems that the possible mechanism of the osteoprotective effect of AME during chronic intoxication with this toxic element involves normalization of the concentrations of calciotropic hormones and Klotho in the serum and improvement of the homeostasis of Ca and P_i. This study provided further evidence that chokeberry products may be an effective strategy in counteracting the unfavourable effects of chronic low-to-moderate exposure to Cd. Full article

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for causing the Coronavirus disease 2019 (COVID-19) outbreak. While mutations cause the emergence of new variants, the ancestral SARS-CoV-2 strain is unique among other strains. Methods: Various clinical parameters, the activity of cathepsin proteases, and the concentration of various proteins were measured in urine samples from COVID-19-negative participants and COVID-19-positive participants. Urinary extracellular vesicles (uEVs) were isolated from urine samples from the two groups and used for proteomic analysis and subsequent pathway analyses. Results: Activity levels of cathepsin S and L were greater in the urine of COVID-19-positive participants. The concentration of C-reactive protein, transmembrane serine protease 2, and klotho protein were significantly greater in the urine of COVID-19-positive participants. There was a greater amount of uEVs in the COVID-19 group and klotho protein was found to be enriched in uEVs from the COVID-19 group. Pathway analyses of the proteomics data showed most of the identified proteins were involved in signal transduction, stress response, protein metabolism, and transport. The identified proteins were predominantly associated with cellular membranes and with function of the cytoskeleton, enzyme regulation, and signal transduction. Conclusions: Taken together, our data identify novel urinary biomarkers that could be used to further investigate the long-term effects of SARS-CoV-2 infection. Full article

Background: Among numerous genes that have been a focus of equine genetic research, the KL (Klotho) and ACTN3 (Alpha-actinin-3) genes stand out due to their significant roles in muscle function and overall health, as well as performance ability. Previous studies on Arabian horses and other mammalians have shown that both KL and ACTN3 occur in different isoforms that seem to have different roles in metabolism. The main purpose of this present study was to describe different isoforms (ACTN3, ACTN3-201, ACTN3-202, KL, KL-202, KL-203) expression levels affected by the endurance effort in Arabian horses. Methods: Blood samples were taken from a group of n = 10 Arabian horses taking part in a long-distance 120 km endurance ride. After RNA isolation and reverse transcription, real-time PCR was performed. The expression levels (Relative Quantity, RQ) were calculated using the delta-delta CT method. The results showed surprisingly large differences between different isoforms expression levels which brought us to the conclusion that both KL and ACTN3 genes are suitable genetic markers to measure endurance performance. Moreover, the correlation network analyses showed that the MIOX (myo-inositol oxygenase), SH3RH2 (SH3 domain-containing ring finger 2) and TNNI2 (Troponin I2, fast skeletal type) genes are significantly involved in the endurance effort metabolism. Full article

Background: Aging is characterized by a decline in the cardiovascular hemodynamic response, which may be aggravated by undernutrition. However, no study has evaluated whether low caloric intake may affect cardiovascular hemodynamics and its possible relation with functional capacity and immune response in older adults. Methods: Sixty-one older adults of both genders were enrolled in this study and were classified as normocaloric (n = 18) and hypocaloric (n = 43). All volunteers were evaluated for cardiovascular hemodynamics using impedance cardiography (PhysioFlow^®); functional capacity by the 1′ sit-to-stand test with SpO₂ monitoring; whole-blood analysis using an automated hematocytometer (Sysmex^®); and levels of IL-6, TNF-alpha, IL-10, and Klotho by ELISA. Results: The hypocaloric group presented impaired functional capacity, measured by a reduced number of sit-to-stand repetitions (p < 0.0251) and impaired delta of SpO₂ (p < 0.0307). In contrast, the hypocaloric group presented an improved stroke volume (p < 0.0352), systemic vascular resistance (p < 0.0075), and systemic vascular resistance index (p < 0.0184). In addition, no changes were observed in the whole-blood analysis (p > 0.05) or for IL-6 (p > 0.05), TNF-alpha (p < 0.05), IL-10 (p < 0.05), and Klotho (p > 0.05). Conclusions: A long-term hypocaloric diet in eutrophic older adults’ resulted in an enhanced cardiovascular hemodynamic response but was associated with reduced functional capacity without changes in the immune response. Full article

Aging comes with the loss of muscle and bone mass, leading to a condition known as osteosarcopenia. Circulating, cellular, and tissue biomarkers research for osteosarcopenia is relatively scarce and, currently, no established biomarkers exist. Here we find that osteosarcopenic patients exhibited elevated basophils and TNFα levels, along with decreased aPPT, PT/INR, IL15, alpha-Klotho, DHEA-S, and FGF-2 expression and distinctive bone and muscle tissue micro-architecture and biomarker expressions. They also displayed an increase in osteoclast precursors with a concomitant imbalance towards spontaneous osteoclastogenesis. Similarities were noted with osteopenic and sarcopenic patients, including a lower neutrophil percentage and altered cytokine expression. A linear discriminant analysis (LDA) on models based on selected biomarkers showed a classification accuracy in the range of 61–78%. Collectively, our data provide compelling evidence for novel biomarkers for osteosarcopenia that may hold potential as diagnostic tools to promote healthy aging. Full article

Reducing oxidative stress stands at the center of a prevention and control strategy for mitigating cellular senescence and aging. Kidney disease is characterized by a premature aging syndrome, and to find a modulator targeting against oxidative stress, mitochondrial dysfunction, and cellular senescence in kidney cells could be of great significance to prevent and control the progression of this disease. This review focuses on the pathogenic mechanisms related to the appearance of oxidative stress damage and mitochondrial dysfunction in kidney disease. In this scenario, the anti-aging Klotho protein plays a crucial role by modulating signaling pathways involving the manganese-containing superoxide dismutase (Mn-SOD) and the transcription factors FoxO and Nrf2, known antioxidant systems, and other known mitochondrial function regulators, such as mitochondrial uncoupling protein 1 (UCP1), B-cell lymphoma-2 (BCL-2), Wnt/β-catenin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), transcription factor EB, (TFEB), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Therefore, Klotho is postulated as a very promising new target for future therapeutic strategies against oxidative stress, mitochondria abnormalities, and cellular senescence in kidney disease patients. Full article

α-Klotho (Klotho) is an antiaging hormone with anti-inflammatory and antioxidative properties. Some studies suggest that Klotho increases in response to enhanced oxidative damage and inflammation. Alcoholism is a proinflammatory condition. The aim of this study was to analyze the relationship between Klotho and the serum levels of the inflammatory markers in alcoholic liver disease and to assess its prognostic value. We included 184 alcoholics and 35 age- and sex-matched controls. We determined the serum levels of Klotho, the tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and malondialdehyde (MDA), and routine laboratory variables. Patients were followed-up with during 16 ± 18 months; 67 patients died. Klotho levels were higher among cirrhotics (with KW = 37.00 and p < 0.001) and were related to the Child–Pugh score (with KW = 15.96 and p < 0.001) and to the TNF-α (ρ = 0.28; p < 0.001) and MDA (ρ = 0.21; p = 0.006). The child’s groups were associated with mortality, both in the univariate (with the log-rank = 13.56, p = 0.001, Breslow = 12.33, and p = 0.002) and multivariate (with β = 0.43, p = 0.02, and OR = 1.53 (1.07–2.15)) analyses, also introducing Klotho and the TNF-α as dichotomic variables. However, the independent prognostic value of the Child’s groups was displaced by Klotho when only cirrhotics were considered; Klotho, over the median (574.4 pg/mL), was associated with higher mortality (with p = 0.04 and OR = 2.68 (1.06–6.84)). We conclude that Klotho is increased in liver cirrhosis. It is directly related to TNF-α, MDA, and to mortality in cirrhotics. Full article

Frequently silent until advanced stages, bone fragility associated with chronic kidney disease-mineral and bone disease (CKD-MBD) is one of the most devastating complications of CKD. Its pathophysiology includes the reduction of active vitamin D metabolites, phosphate accumulation, decreased intestinal calcium absorption, renal alpha klotho production, and elevated fibroblast growth factor 23 (FGF23) levels. Altogether, these factors contribute firstly to secondary hyperparathyroidism, and ultimately, to micro- and macrostructural bone changes, which lead to low bone mineral density and an increased risk of fracture. A vitamin D deficiency is common in CKD patients, and low circulating 25(OH)D levels are invariably associated with high serum parathyroid hormone (PTH) levels as well as with bone mineralization defects, such as osteomalacia in case of severe forms. It is also associated with a variety of non-skeletal diseases, including cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, and reduced immunological response. Current international guidelines recommend supplementing CKD patients with nutritional vitamin D as in the general population; however, there is no randomized clinical trial (RCT) evaluating the effect of vitamin D (or vitamin D+calcium) supplementation on the risk of fracture in the setting of CKD. It is also unknown what level of circulating 25(OH)D would be sufficient to prevent bone abnormalities and fractures in these patients. The impact of vitamin D supplementation on other surrogate endpoints, including bone mineral density and bone-related circulating biomarkers (PTH, FGF23, bone-specific alkaline phosphatase, sclerostin) has been evaluated in several RTCs; however, the results were not always translated into an improvement in long-term outcomes, such as reduced fracture risk. This review provides a brief and comprehensive update on CKD-related bone fragility and the use of natural vitamin D supplementation in these patients. Full article

Heart disease is the leading cause of death worldwide. The major cause of heart failure is the death of the myocardium caused by myocardial infarction, detrimental cardiac remodeling, and cardiac fibrosis occurring after the injury. This study aimed at discovering the role of the anti-aging protein α-klotho (KL), which is the co-receptor of fibroblast growth factor-23 (FGF23), in cardiac regeneration, fibrosis, and repair. We found that the anti-apoptotic function of soluble KL in isoproterenol-treated H9c2 cardiomyocytes was independent of FGF23 in vitro. In vivo, isoproterenol-induced cardiac fibrosis and cardiomyocyte and endothelial cell apoptosis were reduced by KL treatment. Moreover, the number of Ki67-positive endothelial cells and microvessel density within the isoproterenol-injured myocardium were increased upon KL treatment. However, by using genetic fate-mapping models, no evident cardiomyocyte proliferation within the injured myocardium was detected with or without KL treatment. Collectively, the cardioprotective functions of KL could be predominantly attributed to its anti-apoptotic and pro-survival activities on endothelial cells and cardiomyocytes. KL could be a potential cardioprotective therapeutic agent with anti-apoptotic and pro-survival activities on cardiomyocytes and endothelial cells. Full article

Systemic sclerosis, a connective tissue disease, is characterized by thickening of the skin, massive fibrosis of internal organs, vasculopathy, and immune system functioning aberration. Recently, vitamin D (VD) deficit, seen almost universally in patients with systemic sclerosis (SSc), has gained much attention. VD metabolism is precisely orchestrated at the level of the kidney by regulators: parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) and their receptors with a FGF23 co-receptor—α-Klotho. The aim of this study was to assess the levels of VD, α-Klotho, FGF23 in SSc patients and to find the relationship between those parameters and disease activity. We enrolled 48 SSc patients with a diffuse variant of SSc and 23 sex- and age-matched healthy volunteers that served as the control group (CG). Patients were characterized by lower level of VD in comparison to CG (19.8 (12.6–28.9) vs. 24.5 (21.3–31.5) ng/mL; p < 0.01), significantly reduced levels of iFGF23 (19.3 (12.1–30.5) vs. 73.9 (59.7–110.2) pg/mL p < 0.001), and similar α-Klotho concentrations (1415 ± 557 vs. 1526 ± 397 pg/mL), respective. None of these parameters correlated with the extent of skin involvement (modified Rodnan Skin Score) and disease activity according to Eustar 2017 guidelines. The FGF23/α-Klotho index was significantly reduced in SSc patients (0.013 (0.0081–0.025) vs. 0.055 (0.038–0.095); p < 0.001), and its log₁₀ correlated (r = 0.35; p < 0.001) with disease activity score (Eular2017). Our data showed that the FGF23/α-Klotho index may be considered as a novel, potential marker of systemic sclerosis activity. Full article