Search Results (116)

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict patient outcomes. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied extensively in cardiovascular disease, but its investigation in PAD remains limited. This study aimed to use explainable statistical and machine learning methods to assess the prognostic value of GDF15 for limb outcomes in patients with PAD. Methods: This prognostic investigation was carried out using a prospectively enrolled cohort comprising 454 patients diagnosed with PAD. At baseline, plasma GDF15 levels were measured using a validated multiplex immunoassay. Participants were monitored over a two-year period to assess the occurrence of major adverse limb events (MALE), a composite outcome encompassing major lower extremity amputation, need for open/endovascular revascularization, or acute limb ischemia. An Extreme Gradient Boosting (XGBoost) model was trained to predict 2-year MALE using 10-fold cross-validation, incorporating GDF15 levels along with baseline variables. Model performance was primarily evaluated using the area under the receiver operating characteristic curve (AUROC). Secondary model evaluation metrics were accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Prediction histogram plots were generated to assess the ability of the model to discriminate between patients who develop vs. do not develop 2-year MALE. For model interpretability, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the relative contribution of each predictor to model outputs. Results: The mean age of the cohort was 71 (SD 10) years, with 31% (n = 139) being female. Over the two-year follow-up period, 157 patients (34.6%) experienced MALE. The XGBoost model incorporating plasma GDF15 levels and demographic/clinical features achieved excellent performance for predicting 2-year MALE in PAD patients: AUROC 0.84, accuracy 83.5%, sensitivity 83.6%, specificity 83.7%, PPV 87.3%, and NPV 86.2%. The prediction probability histogram for the XGBoost model demonstrated clear separation for patients who developed vs. did not develop 2-year MALE, indicating strong discrimination ability. SHAP analysis showed that GDF15 was the strongest predictive feature for 2-year MALE, followed by age, smoking status, and other cardiovascular comorbidities, highlighting its clinical relevance. Conclusions: Using explainable statistical and machine learning methods, we demonstrated that plasma GDF15 levels have important prognostic value for 2-year MALE in patients with PAD. By integrating clinical variables with GDF15 levels, our machine learning model can support early identification of PAD patients at elevated risk for adverse limb events, facilitating timely referral to vascular specialists and aiding in decisions regarding the aggressiveness of medical/surgical treatment. This precision medicine approach based on a biomarker-guided prognostication algorithm offers a promising strategy for improving limb outcomes in individuals with PAD. Full article

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: The purpose of this study was to investigate the effects of a 16-week exercise program combining aerobic and resistance training on body composition, growth differentiation factor-15 (GDF-15), apelin-12, and interleukin-15 (IL-15) in older Korean women according to obesity status. Methods: Participants were divided into obesity (n = 15) and normal-weight groups (n = 14). A walking exercise was performed at 60–70% heart rate reserve (RPE 13–15). The bodyweight resistance exercises were progressively intensified over 16 weeks. Analysis methods included two-way repeated measures ANOVA, ANCOVA, and paired and independent t-tests. Results: Significant main effects of time and group were observed in body weight (p < 0.001), and both groups demonstrated significant within-group reductions in body mass index (BMI) (obese: p < 0.001; normal-weight: p < 0.05), along with significant between-group differences (p < 0.001). The percentage of body fat significantly decreased over time (p < 0.01) and differed between groups (p < 0.001). GDF-15 exhibited a significant group × time interaction (p < 0.05) and a main group effect (p < 0.05). Although no statistically significant changes were observed in Apelin-12 levels, an opposite trend was identified between groups, with an increase in the obese group and a decrease in the normal-weight group. For IL-15, no significant interaction effect was found between the groups. Conclusions: The 16-week combined exercise intervention improved key markers of body composition, particularly in obese older women, and led to increased GDF-15, indicating potential metabolic benefits. While changes in apelin-12 and IL-15 were not statistically significant, the findings support the utility of combined exercise for mitigating fat accumulation and promoting healthy aging in older adults. Full article

Peripheral artery disease (PAD) is associated with an elevated risk of major adverse cardiovascular events (MACE). Despite this, few reliable biomarkers exist to identify patients at heightened risk of MACE. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine implicated in inflammation, atherosclerosis, and thrombosis, has been broadly studied in cardiovascular disease but remains underexplored in PAD. This study aimed to evaluate the prognostic utility of GDF15 for predicting 2-year MACE in PAD patients using explainable statistical and machine learning approaches. We conducted a prospective analysis of 1192 individuals (454 with PAD and 738 without PAD). At study entry, patient plasma GDF15 concentrations were measured using a validated multiplex immunoassay. The cohort was followed for two years to monitor the occurrence of MACE, defined as stroke, myocardial infarction, or death. Baseline GDF15 levels were compared between PAD and non-PAD participants using the Mann–Whitney U test. A machine learning model based on extreme gradient boosting (XGBoost) was trained to predict 2-year MACE using 10-fold cross-validation, incorporating GDF15 and clinical variables including age, sex, comorbidities (hypertension, diabetes, dyslipidemia, congestive heart failure, coronary artery disease, and previous stroke or transient ischemic attack), smoking history, and cardioprotective medication use. The model’s primary evaluation metric was the F1 score, a validated measurement of the harmonic mean of the precision and recall values of the prediction model. Secondary model performance metrics included precision, recall, positive likelihood ratio (LR+), and negative likelihood ratio (LR-). A prediction probability histogram and Shapley additive explanations (SHAP) analysis were used to assess model discrimination and interpretability. The mean participant age was 70 ± SD 11 years, with 32% (n = 386) female representation. Median plasma GDF15 levels were significantly higher in PAD patients compared to the levels in non-PAD patients (1.29 [IQR 0.77–2.22] vs. 0.99 [IQR 0.61–1.63] pg/mL; p < 0.001). During the 2-year follow-up period, 219 individuals (18.4%) experienced MACE. The XGBoost model demonstrated strong predictive performance for 2-year MACE (F1 score = 0.83; precision = 82.0%; recall = 83.7%; LR+ = 1.88; LR− = 0.83). The prediction histogram revealed distinct stratification between those who did vs. did not experience 2-year MACE. SHAP analysis identified GDF15 as the most influential predictive feature, surpassing traditional clinical predictors such as age, cardiovascular history, and smoking status. This study highlights GDF15 as a strong prognostic biomarker for 2-year MACE in patients with PAD. When combined with clinical variables in an interpretable machine learning model, GDF15 supports the early identification of patients at high risk for systemic cardiovascular events, facilitating personalized treatment strategies including multidisciplinary specialist referrals and aggressive cardiovascular risk reduction therapy. This biomarker-guided approach offers a promising pathway for improving cardiovascular outcomes in the PAD population through precision risk stratification. Full article

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common malignancy with unsatisfactory survival rates, highlighting the need for reliable biomarkers to improve its diagnosis and prognosis. Growth differentiation factor 15 (GDF15), a protein implicated in various cancers, has not been thoroughly investigated in LSCC. This study aimed to evaluate the significance of GDF15 expression in LSCC by integrating immunohistochemical analysis of archival tissue samples with RNA sequencing data from public databases (TCGA and GEO) to provide comprehensive clinical insights. Methods: We analyzed archival tissue samples from 65 patients with LSCC using immunohistochemistry and evaluated GDF15 expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Statistical analyses included Kaplan–Meier survival analysis and Cox proportional hazards regression to assess the correlation between GDF15 expression, clinicopathological variables, and survival outcomes. Results: GDF15 expression did not significantly differ between tumor and adjacent normal tissues. However, in the tissue macroarray (TMA) cohort, high GDF15 expression was significantly associated with a lower TNM stage and less advanced pT status. Kaplan–Meier analysis revealed that high GDF15 expression correlated with reduced overall survival in the TMA cohort, suggesting its utility in risk stratification. Multivariate analysis identified GDF15 as an independent prognostic factor for disease-free survival in LSCC. Conclusions: Our findings suggest that GDF15 may serve as a prognostic biomarker for LSCC, particularly in early-stage disease. Elevated GDF15 levels, which are associated with poorer overall survival, could be integrated into diagnostic panels to enhance risk stratification and inform treatment decisions. Furthermore, GDF15 may be a promising target for therapeutic intervention. Further research is warranted to validate these results and explore their potential in clinical practice. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic progressive hepatopathy in children, and the identification of non-invasive biomarkers is urgently needed. Growth differentiation factor 15 (GDF15) was associated with MASLD in adults. In this study, we investigated the circulating and hepatic levels of GDF15 and their association with liver damage in pediatric MASLD and in a murine model. This observational study included 158 children with biopsy-proven MASLD. Patients with MASLD were categorized into two groups based on steatohepatitis (MASH) presence and evaluated for GDF15 circulating levels, while GDF15 hepatic levels were assessed only in a subset of patients. Children with MASLD exhibited higher levels of circulating GDF15 compared to the controls. Moreover, the MASH subgroup had significantly higher values of GDF15 compared to the Not-MASH subgroup. The GDF15 levels in the MASH subgroup showed a positive correlation with fibrosis. Finally, the hepatic expression of the GDF15 gene correlated with GDF15 circulating levels and with the hepatic expression of the COL1A1 and COL3A1 genes in 15 children with MASLD. In conclusion, our study demonstrated that GDF15 levels are associated with liver damage, reinforcing the potential role of GDF15 as a biomarker for MASLD-related fibrosis in children. Full article

Background: Type 2 diabetes (T2D patients) have a 74% increased risk of heart failure (HF), but traditional HF biomarkers lack sensitivity in early disease detection. Increased epicardial adipose tissue volume (EATv) is associated with cardiovascular risk in T2D, and novel biomarkers such as growth differentiation factor 15 (GDF15), Galectin-3, and soluble suppression of tumorigenicity 2 (sST2) are inflammation biomarkers linked to HF. Methods: We investigated associations between EATv, inflammation biomarkers, and the effect of metabolic control in 14 healthy controls (HCs) and 36 newly diagnosed T2D patients both before (poor glycemic control, PGC) and after 12 months of glycemic optimization (good glycemic control, GGC). EATv indexed to body surface area (iEATv) was quantified by multidetector computed tomography, and biomarker levels were measured by immunoassays. Results: PGC patients had higher iEATv (59.53 ± 21.67 vs. 36.84 ± 16.57 cm³/m², p = 0.0017) and elevated GDF15, Galectin-3, and sST2 levels (all p < 0.05) than HC subjects. The glycemic optimization reduced iEATv (p = 0.0232) and sST2 (p = 0.048), while GDF15 and Galectin-3 remained unchanged. Multivariable analysis confirmed independent associations between iEATv, GDF15 (β = 0.27, p = 0.027) and sST2 (β = 0.29, p = 0.02). Conclusions: These results support the link between systemic inflammation, EAT expansion, and cardiac dysfunction, and they point to the role of epicardial fat in early HF risk of T2D patients. Full article

Background: Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β (TGF-β) superfamily, is upregulated under cellular stress conditions and has emerged as a potential biomarker for metabolic disorders. However, its expression in relation to diabetes and obesity across different demographic groups remains understudied. This study investigated the association between plasma GDF-15 levels, diabetes mellitus, and obesity in individuals of varying ages, ethnicities, and genders. Methods: In a cross-sectional study, plasma GDF-15 concentrations were measured in 2083 participants enrolled in the Kuwait Diabetes Epidemiology Program (KDEP). The dataset included anthropometric, clinical, biochemical, and glycemic markers. Multivariate regression analysis was used to examine associations between GDF-15 levels and metabolic phenotypes. Results: Mean plasma GDF-15 levels were significantly higher in males than females (580.6 vs. 519.3 ng/L, p < 0.001), and in participants >50 years compared to those <50 years (781.4 vs. 563.4 ng/L, p < 0.001). Arab participants had higher GDF-15 levels than South and Southeast Asians (597.0 vs. 514.9 and 509.9 ng/L, respectively; p < 0.001). Positive correlations were found with BMI, waist and hip circumferences, blood pressure, insulin, and triglycerides; negative correlations were observed with HDL cholesterol. Median regression indicated that elevated GDF-15 levels were independently and significantly associated with male gender, older age, obesity, diabetes, and insulin resistance. Adjusted median regression indicated that male gender (β = 30.1, 95%CI: 11.7, 48.5), older age (β = 9.4, 95%CI: 8.0, 10.7), and insulin resistance (β = 7.73, 95%CI: 1.47, 14.0) indicated a significant positive association with GDF-15. South Asian participants (β= −41.7, 95%CI: −67.2, −16.2) had significantly but Southeast Asian participants (β= −23.3, 95%CI: −49.2, 2.56) had marginally significantly lower GDF-15 levels compared to participants of Arab ethnicity. Conclusions: Higher GDF-15 levels are associated with age, male gender, Arab ethnicity, obesity, and diabetic traits. These findings support the potential role of GDF-15 as a biomarker for metabolic disorders, particularly in high-risk demographic subgroups. Full article

Growth Differentiation Factor 15 (GDF15), also known as non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) or macrophage inhibitory cytokine 1 (MIC-1), is a stress- and inflammation-induced cytokine distantly related to the TGF-β superfamily. Its highly elevated levels showed close association with various pathological conditions, making it an emerging biomarker of disease prognosis. However, most GDF15-mediated effects under normal physiology and various pathological conditions are poorly understood. This is partly because the only known GDF15 receptor is exclusively localized in the brain, and how GDF15 functions peripherally is currently unknown. Mounting recent evidence has shown GDF15’s critical role in fibrosis in multiple organs, such as the liver, lung, and kidney. Evidence further suggests that it can either contribute to fibrosis by promoting inflammation and fibroblast activation or confer protective effects by modulating the immune response and mitigating fibrosis severity. Thus, the exact role of GDF15 in fibrosis can vary depending on the organ involved and the specific disease context. For example, increased GDF15 in idiopathic pulmonary fibrosis (IPF) promotes fibrosis via fibroblast activation and collagen deposition. Conversely, GDF15 might have a protective role in liver fibrosis, with decreased GDF15 levels causing increased fibrosis severity, while GDF15 treatment ameliorates fibrosis. Due to its close association with fibrosis, GDF15 is being investigated as a potential biomarker for disease severity and monitoring treatment response. However, further research unraveling its mechanisms of action is needed to explore the potential of GDF15 as a therapeutic target for treating fibrosis, either by modulating its expression or utilizing its immunomodulatory properties. This review marshals the limited studies addressing the recently appreciated differential role of GDF15 in regulating the fibrotic process in different organs. The review also discusses the aspects of further research needed to highlight GDF 15 as a novel predictor and therapeutic target for fibrosis in different organs. Full article

Background/Objectives: Cellular aging represents a crucial element in the progression of musculoskeletal diseases, contributing to muscle atrophy, functional decline, and alterations in bone turnover, which promote fragility fractures. However, knowledge about expression patterns of factors potentially involved in aging and senescence at the tissue level remains limited. Our pilot study aimed to characterize the expression profile of cell cycle regulators, factors released by aged cells, and sirtuin 1 (SIRT1) in the muscle tissue of 26 elderly patients undergoing hip arthroplasty, including 13 with low-energy fracture and 13 with osteoarthritis (OA). Methods: The mRNA expression levels of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), cyclin-dependent kinase inhibitor 2A (CDKN2A), p53, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-15 (IL-15), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3), growth differentiation factor 15 (GDF15), and SIRT1 were evaluated in muscle tissue by qRT-PCR. In addition, immunohistochemistry and Western blotting analysis were conducted to measure the protein levels of SIRT1. Results: A marked muscle atrophy was observed in fractured patients compared to the OA group, in association with an up-regulation of cell cycle regulators and factors released by the aged cells. The expression of matrix metallopeptidase 3 (MMP3), plasminogen activator inhibitor 1 (PAI-1), and fas cell surface death receptor (FAS) was also investigated, although no significant differences were observed between the two experimental groups. Notably, SIRT1 expression was significantly higher in OA patients, confirming its role in maintaining muscle health during aging. Conclusions: Further studies will be needed to clarify the role of SIRT1 in the senescence characteristic of age-related musculoskeletal disorders, counteracting the muscle atrophy that predisposes to fragility fractures. Full article

Background and Objectives: Despite the latest advancements in interventional procedures and pharmacological therapy, the incidence of heart failure and death rate following an acute myocardial remain unacceptably high. This study was designed in response to the limited and conflicting literature data regarding the diagnostic and prognostic role of modern inflammatory biomarkers in patients with coronary artery disease. Materials and Methods: We conducted a case–control, prospective observational study. A total of 145 patients were analyzed, of whom 105 patients had an acute coronary syndrome diagnosis and represented the study group, while 40 patients with a chronic coronary syndrome diagnosis represented the control group. This study investigates the diagnostic and prognostic role of the interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), Growth differentiation factor 15 (GDF-15), and classic biomarkers in patients with ischemic coronary heart disease. Results: IL-1β exhibited a prognostic role, being significantly correlated with a left ventricular ejection fraction below 30%. GDF-15 plays a dual role, as a cardio-inflammatory biomarker, being significantly correlated with both N-terminal pro-brain natriuretic peptide (NT-proBNP), and IL-1β, IL-6, and CRP. At the same time, GDF-15 represents a surrogate marker for renal dysfunction. According to the ROC analysis, patients at high mortality risk can be identified with adequate accuracy by cardiac troponin, GDF-15, and IL-10, in addition to NT-proBNP. Logistic regression models confirmed NT-proBNP and IL-10 as mortality predictors. Conclusions: IL-1β stands out for its significant prognostic role, while IL-6 did not demonstrate a diagnostic or prognostic role in acute myocardial infarction patients. IL-10 demonstrated superior predictive value in terms of fatal prognosis compared with the other modern biomarkers. GDF-15 is representative of a multivalent biomarker involved in inflammation, heart failure, and renal dysfunction. Full article

(1) Background: Prompt acute coronary syndrome (ACS) recognition remains challenging. This study evaluated the diagnostic and prognostic performance of novel biomarkers for non-ST-elevation myocardial infarction (NSTEMI). (2) Methods: Patients with suspected ACS presenting to Heidelberg University Hospital’s Emergency Department between August 2014 and February 2023 were analyzed. The biomarker panel included high-sensitivity cardiac troponin T (hs-cTnT), cardiac myosin-binding protein C (cMyBP-C), pro-B-type natriuretic peptide (proBNP), total N-terminal pro-B-type natriuretic peptide (t-NtproBNP), Angiotensin II (Ang2), Bone morphogenetic protein 10 (BMP10), Endothelial cell-specific molecule 1 (ESM1), fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor 15 (GDF15), and Copeptin. Negative predictive values (NPVs), sensitivities, and area under the curve (AUC) values were calculated for NSTEMI discrimination. Effectiveness and prognostic performance were assessed based on cardiovascular events at 30 days and 1 year. (3) Results: Of 1765 patients, 212 (12%) were diagnosed with NSTEMI. The European Society of Cardiology (ESC) 0/1 h and 0/3 h algorithms achieved sensitivities of 100% and 96.8%, NPVs of 100% and 99.3%, and effectiveness values of 54.8% and 66.0%. Hs-cTnT (AUC: 0.922) and cMyBP-C (AUC: 0.917) exhibited the highest diagnostic accuracy, followed by FABP3 (AUC: 0.759) and Copeptin (AUC: 0.624). Other biomarkers had lower performance (AUC: 0.516–0.617). At 1 year, event rates ranged from 0.0% to 3.4%, with the ESC algorithms demonstrating superior prognostic performance (0.8%, 2.4%). (4) Conclusions: The ESC 0/1 h and 0/3 h algorithms remain the most effective NSTEMI diagnostic strategies, balancing high sensitivity, prognostic reliability, and effectiveness. Among novel biomarkers, only cMyBP-C demonstrated comparable accuracy to hs-cTnT, supporting its potential as an adjunct to troponin assays. Full article

Systemic sclerosis, a connective tissue disease of unknown etiology and unpredictable outcomes, is characterized by the fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The disease is classified into two main subtypes, which differ in clinical presentation, complications, and prognosis. While several biomarkers have been proposed to distinguish between these subtypes, none have achieved high sensitivity and specificity. The search for dependable markers that can differentiate between the two primary subtypes of systemic sclerosis continues. To address this gap, our study evaluated the utility of novel cardiac biomarkers, including growth differentiation factor 15 (GDF15), galectin-3, mid-regional pro-atrial natriuretic peptide (MR-proANP), glutathione S-transferase π, mid-regional adrenomedullin, and soluble urokinase plasminogen activator receptor (suPAR), in a cohort of 79 patients with both lcSSc and dSSc subtypes. The results demonstrated a significant elevation of GDF15 (medians: 2.07 vs. 1.10 ng/L; p < 0.001) and MR-proANP (92.55 vs. 65.60 pmol/L; p < 0.05) levels in SSc patients compared to healthy controls. Moreover, GDF15 (1.65 vs. 2.34 ng/mL; p < 0.05), MR-proANP (80.87 vs. 109.27 pmol/L; p < 0.05), and suPAR (1.83 vs. 2.44 ng/mL; p < 0.05) levels were notably higher in patients with dSSc compared to those with lcSSc. In the ROC analysis, only GDF-15, MR-proANP, and suPAR proved to have a statistically significant area under the curve (AUC). Patients with the GDF-15 ≥ 2182 ng/mL, MR-prANP ≥ 85.808 pmol/L, and suPAR ≥ 2.315 ng/mL have more than six-, eight-, and seven-times-higher odds for dcSSc, respectively. These findings highlight the potential of GDF15, suPAR, and MR-proANP as biomarkers for differentiating between the two main subtypes of systemic sclerosis. Full article

Biological aging is normally associated with greater physiological changes which predispose individuals to adverse outcomes. In this way, the evaluation of vulnerability biomarkers and their relationships with other health biomarkers could contribute to the promotion of interventions and the improvement of older adults’ quality of life. Thereby, this study aimed to compare vulnerability biomarkers (Growth Differentiation Factor 15 (GDF-15), General Functional Fitness Index (GFFI), and frailty phenotype) and their influence on health markers (blood biochemistry, body composition, and hemodynamic variables) in middle-aged and older female adults. Methods: A cross-sectional observational study was conducted with community-dwelling females aged 54–84 with at least 6 months of experience with physical training. The participants were categorized based on functional fitness, frailty phenotype, and GDF-15 quartiles. The General Functional Fitness Index (GFFI) was assessed using the AAHPERD test battery, while frailty phenotype was determined using Fried’s criteria. GDF-15 levels were measured through ELISA. Results: A higher training status (TS) showed better functional fitness and favorable biochemical profiles, including lower total cholesterol (p = 0.006, η²p = 0.253), LDL cholesterol (p = 0.001, η²p = 0.346), triglycerides (p = 0.048, η²p = 0.195), and systolic blood pressure (p = 0.001, η²p = 0.333). Individuals classified as robust (non-frail) had better physical performance and lower total cholesterol (p = 0.002, η²p = 0.306) and LDL cholesterol (p = 0.014, η²p = 0.216) compared to those classified as frail and pre-frail. The GDF-15 quartile did not present differences in health markers between groups. Conclusions: These findings suggest that GFFI may be considered a health biomarker for middle-aged and female older adults while highlighting the need for further research on the role of biomarkers of vulnerability and healthy aging. Full article