Search Results (10,809)

Background: Lattice Radiotherapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions >/=7cm was on the extent of shrinkage following palliative LRT (mean 50%) and assessment of its effect duration (: mean 6 months). Herewith we present an updated analysis of our single-center LRT cohort, with a focus on LRT outcome across diagnoses and applied LRT regimens. Methods: We assessed the clinical outcome following LRT in 66 patients treated for 81 lesions between 01.2022 and 05.2025. LRT protocols included simultaneous integrated boost (sib-) LRT in 49 lesions (5 × 4–5 Gy to the entire mass with sib of 9–13 Gy to lattice vertices). Alternatively mainly in pre-irradiated and/or very large lesions—a single-fraction stereotactic LRT (SBRT-LRT) of 1 × 20 Gy to vertices only was delivered to 26 lesions. In six cases with modest response to single fraction SBRT-LRT, the sib-LRT schedule was added 4–8 weeks later. Results: The median age was 68 years (18–93). Main tumor locations were abdomino-pelvic (n = 34) and thoracic (n = 17). Histopathological diagnoses included carcinoma (n = 34), sarcoma (n = 31), and melanoma (n = 16). 31% of all lesions have been previously irradiated. 73% of cases underwent concurrent or peri-LRT systemic therapy. The mean/median overall survival (OS) time of the cohort was 7.6/4.6 months (0.4–40.2), 11.9/5.8 months in 16/66 alive, and 6.4/4.3 months in deceased patients, respectively. 82% of symptomatic patients reported immediate subjective improvement (PROM), with a lifelong response duration in most cases. Progressive disease (PD: >10% increase in initial volume) was found in 9%, stable disease (SD +/−10% of initial volume) in 19% of scanned lesions, and shrinkage (>10% reduction in initial volume) in 75%, with a mean/median tumor volume reduction of 51/60%. The extent of shrinkage was found to be 11–30%/31–60%/61–100% in 38/24/38% of lesions. Response rates (PD, SD, shrinkage) following the two applied LRT regimens, as well as those related to sarcoma and carcinoma diagnoses, were found to be comparable. Treatment tolerance was excellent (G0-1). Conclusions: Palliative LRT provides rapid subjective relief in ~80% of symptomatic patients. Radiologic shrinkage was stated in 75% of FU-scanned lesions, with a lifelong effect duration in most patients. LRT was found effective across histologies, with a similar extent of shrinkage in carcinoma and sarcoma following 1F SBRT- and 5F sib-LRT regimens, respectively. Full article

Background: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the developed world, and the approved products for geographic atrophy (GA), a late-stage form of dry AMD, have shown limited efficacy and require frequent administration. Therefore, longer-lasting therapies with improved efficacy would be a welcome addition to AMD treatment. One potential therapeutic is ONL1204, a small peptide inhibitor of the Fas receptor that has prevented cell death and inflammation in retinal disease models. This study characterizes the pharmacokinetics (PK) and durability of protection conferred by ONL1204. Methods: Ocular pharmacokinetic profiles were generated over 3 months in rabbit and minipig following a single intravitreal (IVT) injection of ONL1204 at multiple doses. Ocular pharmacodynamics were evaluated in two models: a rabbit model using a single IVT injection of ONL1204 with a delayed sodium iodate challenge coupled with fluorescein angiography to quantify RPE loss, and a chronic mouse model that reflects key features of dry AMD disease pathology to assess the efficacy of repeat IVT administrations of ONL1204. Results: ONL1204 had prolonged residence in the ocular tissues of rabbit and minipig, with a vitreous humor half-life of over 100 days. ONL1204 demonstrated significant protection of the retinal pigment epithelium (RPE) in the rabbit sodium iodate model. In the chronic mouse model, two administrations of ONL1204 preserved RPE morphology, reduced caspase-8 activity, and decreased inflammation. Conclusions: These data represent key characteristics of ONL1204, highlighting its clinical potential as a therapeutic for chronic retinal diseases, including GA. Full article

Children with COVID-19 typically experience milder symptoms and lower hospitalization rates, though severe cases do occur. Understanding age-related immune responses is crucial for future preparedness. We characterized immune response dynamics to SARS-CoV-2 in 145 samples from 119 pediatric patients (<18 years) with confirmed infection, assessed at four distinct time points: <14 days, 14 days–3 months, 3–6 months, and 6–12 months post-infection. At infection, patients presented increased activated T-cells, higher levels of exhaustion (i.e., PD-1⁺), lower numbers of unswitched memory B-cells, and increased antibody-secreting cells (ASCs). Both humoral and cellular anti-SARS-CoV-2 responses increased over time (all patients showed measurable responses in the last assessment). Asymptomatic/mildly symptomatic patients (58.6%) showed increased specific cellular responses from infection onwards, along with enriched memory B-cell subsets (but not ASCs), and distinct T-cell activation profiles. Children with severe disease were younger, predominantly boys, displayed altered T/B-cell ratios, and reduced PHA responses when infected. Compared to adolescents, younger children showed lower antibody titers and weaker cellular responses to SARS-CoV-2, possibly underlining the higher prevalence of severe manifestations in younger children. Our study illustrates important age-, gender-, and disease severity-dependent variations in immune responses to SARS-CoV-2, which can be helpful in improving patient management and immunization strategies adjusted to age groups. Full article

Background: Article 32 of the Italian Constitution guarantees the right to health for all citizens, including detainees. Prison populations face unique health challenges due to high-risk lifestyles, psychosocial stressors, and limited access to care. This study aimed to investigate the burden of chronic diseases and associated risk factors among male inmates in a central Italian prison. Methods: This cross-sectional study was conducted in accordance with STROBE guidelines at Giuseppe Pagliei Prison in Frosinone, Central Italy, from May 2022 to May 2023. A total of 477 adult male inmates underwent systematic clinical evaluations and medical record reviews. Demographic and health data were analyzed to determine the prevalence of chronic conditions and related risk factors. Results: Participants (mean age 47.3 ± 13.1 years; 69.6% Italian, 30.4% international, mainly Eastern European and African) presented on average 1.8 chronic conditions. The most frequent diagnoses were psychiatric disorders (19.9%), cardiovascular diseases (17.2%), and osteoarticular disorders (14.5%). Disease burden correlated with aging, unhealthy lifestyles, and incarceration-related stressors. Tobacco smoking was highly prevalent. Conclusions: Male inmates show a considerable and partly preventable burden of chronic disease. Broader policy measures, including alternative sentencing and community-based rehabilitation, may mitigate the health impact of imprisonment while ensuring public safety. Adequate prison healthcare remains a public health priority and a constitutional and human rights obligation. Full article

Background: Ampullary adenocarcinoma is a rare cancer for which there are no standard adjuvant treatment recommendations due to the lack of randomized clinical trials. The primary aim of this analysis is to investigate the efficacy of adjuvant FOLFIRINOX treatment in patients with resected ampullary adenocarcinoma. Materials and Methods: This multicenter retrospective cohort study was conducted at 15 institutions in Turkey between August 2007 and January 2024, involving 211 patients with resected, non-metastatic ampullary adenocarcinoma receiving adjuvant chemotherapy with various chemotherapy regimens with or without chemoradiation. Clinicopathological and treatment-related parameters were recorded. Disease-free survival (DFS) and overall survival (OS) were analyzed by using Kaplan–Meier estimates. Cox proportional hazards regression was used to identify covariates associated with OS. Results: The median follow-up time was 52 months, and 116 patients (55.2%) were alive at the time of the analysis. The median age was 61 years (32–82). mFOLFIRINOX was administered to 16.6% of the patients (n = 35). The 3-year DFS rate was 79.41% in the FOLFIRINOX-treated arm and 53.9% in the other treatment arm (p = 0.034 for mDFS). The median OS was non-reached in patients receiving mFOLFIRINOX treatment, while it was 51 months in patients receiving other treatments (p = 0.071). While no statistically significant results were reached, a trend toward statistically significant survival times was observed in the FOLFIRINOX arm. After adjustment for other prognostic parameters, mFOLFIRINOX remained an independent statistically significant parameter for better OS (HR; 95% CI: 3.24; 1.02–10.9; p = 0.046). Conclusions: FOLFIRINOX treatment has shown efficacy in the adjuvant treatment of ampullary cancer, independent of histological subtype. The findings should be validated in large prospective trials. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrosing interstitial disease that incurs significant healthcare costs due to diagnostic and treatment needs. This study aimed to estimate healthcare expenses related to IPF diagnosis, treatment, and follow-up, including factors affecting overall expenditure. Methods: This retrospective cohort study included 276 IPF patients from a tertiary hospital (2013–2022). Diagnostic and treatment costs were analyzed, including antifibrotic medications (pirfenidone and nintedanib), diagnostic tests (pulmonary function tests and performance evaluation tests), and interventions (fiberoptic bronchoscopy, imaging modalities). Costs in Turkish Lira were converted to United States dollars. Statistical analysis was performed using non-parametric tests to evaluate expenditure correlations with demographic, clinical, and treatment parameters, which included the Mann–Whitney and Spearman Rank Correlation tests when appropriate. Results: The median healthcare expenditure was USD 429.1 (9.13–21,024.57). Inpatient costs (USD 582.67; USD 250.22 to USD 1751, 25th and 75th percentile, respectively) were higher than outpatient costs (USD 192.36; USD 85.75 to USD 407.47, 25th and 75th percentile, respectively). Antifibrotic regimens did not differ significantly in cost or duration (Z = 0.657; p = 0.511) (mean pirfenidone duration: 1.1 ± 1.0 years; mean nintedanib duration: 0.6 ± 0.9 years). Diagnostic tests, particularly pulmonary function tests (PFT) (p: 0.001, Rho: 0.337), diffusing capacity of the lungs for carbon monoxide (DLCO) (p: 0.001, Rho: 0.516), and high-resolution computed tomography (HRCT) (p: 0.001, Rho: 0.327), were the primary drivers of costs. Longer treatment duration was positively correlated with expenditure (Rho: 0.264, p: 0.001 and Rho: 0.247, p: 0.006 for pirfenidone and nintedanib, respectively) while age showed a weak negative correlation (Rho = −0.184, p = 0.002). Gender and type of antifibrotic regimen did not show any significant effect on costs. Discussion: Diagnostic and follow-up testing were the main contributors to costs, driven by reimbursement requirements and the progressive nature of IPF. Antifibrotic medications, although expensive, provided clinical stability, potentially reducing hospitalization needs but increasing long-term care expenses. Variations in healthcare systems affect expenditures, with Turkey’s universal coverage lowering costs compared to Western countries. The study’s main limitations include being a single-center, retrospective study and its inability to include comorbidities and disease severity in the statistical analysis. Conclusions: IPF management is resource-intensive, with diagnostic tests and follow-up driving costs independent of demographics and treatment modality. Anticipating higher expenditures with prolonged survival and evolving treatment options is crucial for healthcare budget planning. Preparation of healthcare policies accordingly to these observations, which must include an overall increase in cost due to treatment duration and survival, remains a crucial aspect of budget control. Full article

Streptococcus pneumoniae remains a leading cause of invasive diseases, particularly affecting young children and the elderly. Currently, two main types of pneumococcal vaccines are commercially available: polysaccharide vaccine (PPSV23) and conjugate vaccines (e.g., PCV20). Of over 100 identified pneumococcal serotypes, vaccines targeting 24 serotypes covered by PPSV23 and PCV20 (19 serotypes overlap between the two vaccines) have been developed, with serotype distribution varying by geography, age, and time. The immune response to pneumococcal vaccines differs across serotypes, vaccine types (polysaccharide vs. conjugate), and host factors. Quantitative methods for antibody assessment—particularly newer high-throughput assays—have emerged since 2000 to address limitations in conventional approaches. However, these methods have not been comprehensively reviewed. This scoping review aimed to systematically map the existing literature on quantitative methods used to assess antibody responses to pneumococcal vaccines. Specific objectives included the following: 1. summarizing conventional and novel quantitative immunoassays; 2. evaluating the current state of validation and application of these methods; 3. identifying knowledge gaps and methodological challenges. We followed the PRISMA-ScR guidelines. We included the following: 1. peer-reviewed, open-access papers related to immunoassays used for pneumococcal antibody assessment; 2. articles written in English; 3. Studies published between 2000 and 2023. We excluded the following: 4. studies focusing on other pathogens, employing different analytical methods, or using animal models. Articles meeting the eligibility criteria were primarily retrieved from PubMed and Scopus. If free full-text versions were unavailable there, Google Scholar or the original journal databases were consulted. All references were exported to EndNote 20 for further management. At the beginning of the review, a data-charting form was developed based on prior studies and commonly addressed themes. Additional charts were created to accommodate newly identified variables during the review. All charting tools were reviewed and finalized through discussion among all research team members. The included studies were classified into five thematic groups: 1. general descriptions of quantitative assessment methods, 2. assay development and validation, 3. comparative studies, 4. technical details of assay development, 5. interpretation of assay application findings. Of 1469 articles from PubMed and 2946 articles from Scopus initially identified, 55 articles met the inclusion criteria. The earliest methods included radioimmunoassays, later replaced by WHO-standardized ELISA. While ELISA remains the gold standard, it is limited by labor, cost, and throughput. Multiplex immunoassays (MIAs), including Luminex-based platforms, have demonstrated advantages in efficiency and scalability. However, many MIAs did not initially meet WHO validation criteria. More recent assays show an improved performance, yet interlaboratory variability and lack of standardized protective thresholds remain major limitations. This review provides the first comprehensive mapping of quantitative antibody assessment methods for pneumococcal vaccines. Although ELISA continues to serve as the benchmark, MIAs represent a promising next-generation approach. Continued efforts are needed to harmonize assay validation protocols and establish global standards for protective thresholds, which will enhance the reliability of vaccine efficacy monitoring across diverse populations. Full article

This retrospective longitudinal study evaluated the significance of cholestasis syndrome and the diagnosis of primary sclerosing cholangitis (PSC) in inflammatory bowel disease (IBD) patients from a tertiary center in Romania. Methods: From 2011 to 2022, 3767 patients suspected for IBD were evaluated, with 2499 confirmed cases. Of these, 34 patients (1.36%) had an IBD-PSC phenotype. Of the IBD-PSC cases, 56% were associated with UC and 44% with CD. Results: Enzymatic cholestasis was observed in 13.3% of IBD patients, with gamma-glutamyl transpeptidase (GGT) elevated in 70.2% and alkaline phosphatase (ALP) in 51.3%. However, only 10.2% of the patients with enzymatic cholestasis were diagnosed with PSC. Other liver diseases identified included metabolic-associated steatotic liver disease (MASLD), chronic viral hepatitis, Primary Biliary Cholangitis, autoimmune hepatitis, and liver neoplasms. A higher incidence of cholangiocarcinoma (11.76% vs. 0.24%, p < 0.001) and liver-related death (8.82% vs. 0.65%, p < 0.001) was found between IBD-PSC patients and those without PSC. PSC-CD patients were diagnosed at a younger age (30.2 vs. 43 years, p < 0.001), had higher rates of severe disease (73.3% vs. 10.5%, p < 0.001), required more biological treatment (60% vs. 15.7%, p < 0.001), and experienced higher mortality (20% vs. 0%, p < 0.001). Discussions: This study represents the most extensive cohort analysis of PSC-IBD patients in Romania and Eastern Europe, highlighting clinical differences between PSC-UC and PSC-CD phenotypes. Conclusions: The regular monitoring of ALP and GGT in IBD patients helps detect liver diseases, including PSC. However, only one in ten patients with IBD and enzymatic cholestasis was diagnosed with PSC. Full article

Down syndrome (DS) is the most common survivable chromosome trisomy, with an incidence of about 1 in 600–700 births. Consequences of chromosome 21 trisomy include developmental delays, congenital cardiac abnormalities, skeletal abnormalities, and age-related dementia of the Alzheimer’s disease (AD) type. Up to 90% of individuals with DS develop dementia symptoms in their 40s or 50s. Because the biological mechanisms involved in DS-related developmental and age-related pathology are less known, animal models consisting of both lower-order and higher-order animals have been developed. We here review the most pertinent and well-studied DS animal models including models developed in C. elegans, Drosophila, zebrafish, and mice. Molecular pathways involved in DS morbidity that were discovered in animal models will also be discussed. Full article

Background and Objectives: Metabolic syndrome (MetS) progresses gradually as individual components accumulate. However, there is limited understanding regarding whether the sequence of component appearance influences disease progression. This study sought to determine the most frequent initial MetS component and evaluate whether this component influences the subsequent risk of developing full MetS. Materials and Methods: We examined data from 6137 participants in the Korean Genome and Epidemiology Study (KoGES), free of MetS at baseline (2001–2002), followed until 2011–2012. Participants were stratified by the first emerging MetS component: abdominal obesity, elevated blood pressure, high fasting glucose, high triglycerides, or low HDL cholesterol. The primary endpoint was progression to full MetS, defined as the development of three or more components. We also assessed transition probabilities between components and sex-specific sequence differences. Results: Abdominal obesity was the most frequent initial metabolic abnormality (31.0%), followed by elevated blood pressure (26.3%), low HDL cholesterol (15.3%), high triglycerides (13.7%), and high fasting glucose (4.9%). Over a median 8.2-year follow-up, participants with initial abdominal obesity exhibited the greatest progression rate to full MetS (44.4%), significantly higher than those with elevated blood pressure (24.8%), high triglycerides (23.0%), high fasting glucose (21.6%), or low HDL cholesterol (9.3%) (all p < 0.001). After controlling for age, sex, smoking status, and baseline BMI, initial abdominal obesity was associated with a 4.77-fold increased risk (95% CI: 3.68–6.18) of developing full MetS compared to initial low HDL cholesterol. Distinct transition patterns were observed: high triglycerides frequently transitioned to low HDL cholesterol (78.1%), while abdominal obesity most often led to elevated blood pressure (52.1%). Marked sex-related differences were also found: abdominal obesity was more common initially among women (41.7% vs. 25.2%), whereas elevated blood pressure was predominant among men (37.6% vs. 21.2%). Conclusions: The initial MetS component strongly predicts progression to full syndrome, with abdominal obesity conferring the highest risk. Early identification and targeted interventions addressing abdominal obesity may effectively prevent MetS and its subsequent complications. Full article

Background: This study investigated the cross-sectional associations of personal and general views on aging, number of non-communicable diseases, and their interactions as cross-sectional predictors of vigorous physical activity. Methods: Participants were 1699 individuals aged 50 years and over (Mean age = 67.79) and living in the community in the UK; 70.8% were women. Participants completed measures assessing Awareness of Age-Related Gains and Losses (AARC-Gains; AARC-Losses; indicators of personal views on aging), Expectations Regarding Aging (ERA; indicator of general views on aging), vigorous physical activity in the last month, non-communicable disease status, and sociodemographic questions. Linear regression models were used. Results: After having adjusted for age, sex, education, marital status, and working status, higher AARC-Gains, lower AARC-Losses, more positive ERA, and fewer non-communicable diseases were cross-sectionally associated with greater likelihood of engagement with vigorous physical activity (Adjusted models Odds Ratio (OR) of 1.08; 0.86; and 1.06, respectively). The interactions of AARC-Gains and AARC-Losses with number of non-communicable diseases as cross-sectional predictors of likelihood of engagement with vigorous physical activity were not statistically significant. The interaction between ERA (i.e., General Views on Aging) and number of non-communicable diseases was a statistically significant cross-sectional predictor of likelihood of engagement with vigorous physical activity (OR = 0.99; p = 0.044). Conclusions: Having more positive and less negative views on aging may prompt vigorous physical activity engagement. Moreover, positive general views of aging may be particularly important for physical activity among those who have one or more non-communicable diseases. Although we cannot infer causality, promoting positive views on aging and decreasing negative views on aging could help fostering active aging, especially among those with physical health conditions. Full article

Background/Objectives: Cardiac Syndrome X (CSX) is associated with significant physical and psychiatric morbidity despite no obvious effect on long-term mortality. Obstructive sleep apnea (OSA) is a prevalent condition in close association with numerous cardiovascular diseases. The precise relation between CSX and OSA remains unclear. The aim of this study is to explore the relation between OSA and CSX, as well as the impact of continuous positive airway pressure (CPAP) therapy on myocardial ischemia. Methods: This single-center prospective cohort study examined patients who were selected consecutively from the Cardiology Outpatient Clinic with angina or angina-equivalent complaints and with ischemia on myocardial perfusion scintigraphy (MPS), and who were subsequently diagnosed with CSX via coronary angiography. Patients with previous myocardial infarction and previous percutaneous coronary intervention or coronary artery by-pass grafting surgery were excluded, since these conditions could not be regarded as CSX. The presence of OSA was explored by polysomnography (PSG). CPAP therapy was applied for three months to those diagnosed with OSA. Following a three-month course of treatment, a myocardial perfusion scintigraphy (MPS) was conducted, to assess myocardial ischemia. The IBM^® SPSS Statistics Version 26 software was employed for the purpose of statistical analysis. Results: Among the 27 consecutive patients (mean age 58.1 ± 9.6 years and 22 female) with CSX 24 patients were found to have OSA according to PSG examination. CPAP therapy was applied to 17 patients (mean age 56.4 ± 8.6 years, 14 female) who accepted to participate in the treatment phase of the study. Following a three-month course of treatment, myocardial ischemia was reduced in 13 of the 17 patients. There were statistically significant correlations between the reduction in myocardial ischemia and patient’s diagnosis of hypertension (p = 0.006), higher serum HDL cholesterol levels (p = 0.009), and adherence to CPAP therapy (p = 0.047). Conclusions: The prevalence of OSA is significantly higher among the patients with CSX compared to the general adult population. In patients with CSX and OSA, improvement in myocardial ischemia was observed in MPS following CPAP therapy. Full article

Oxidative stress is a key contributor to retinal degeneration, as the retina is highly metabolically active and exposed to constant light stimulation. This review explores the crucial roles of cysteine and selenocysteine in redox homeostasis and retinal protection. Cysteine, primarily synthesized via the transsulfuration pathway, is the rate-limiting precursor for glutathione (GSH), the most abundant intracellular antioxidant. Selenocysteine enables the enzymatic activity of selenoproteins, particularly glutathione peroxidases (GPXs), which counteract reactive oxygen species (ROS). Experimental evidence from retinal models confirms that depletion of cysteine or selenocysteine results in impaired antioxidant defense and photoreceptor death. Furthermore, dysregulation of these amino acids contributes to the pathogenesis of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Therapeutic approaches including N-acetylcysteine, selenium compounds, and gene therapy targeting thioredoxin systems have demonstrated protective effects in preclinical studies. Targeting cysteine and selenocysteine-dependent systems, as well as modulating the KEAP1–NRF2 pathway, may offer promising strategies for managing retinal neurodegeneration. Advancing our understanding of redox mechanisms and their role in retinal cell viability could unlock new precision treatment strategies for retinal diseases. Full article

Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34⁺ HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer’s disease (AD), the APPswe/PS1dE9 mouse. At 12 months of age, mice received intracisternal injections of NC (1.39 × 10⁶ MSCs + 5 × 10⁵ HSCs) or vehicle. After 45 days, behavioural testing, immunohistochemical analyses of amyloid plaque density (APD), and cortical gene expression profiling were conducted. NC-treated APP/PS1 mice exhibited preserved object recognition memory and reduced anxiety-like behaviours, contrasting with deficits observed in untreated transgenic controls. Histologically, NC treatment significantly reduced the density of small amyloid plaques (<50 μm²) in the hippocampus and thalamus, and total plaque burden in the thalamus. Gene expression analysis revealed that NC treatment normalised or reversed disease-associated changes in insulin receptor (IR) signalling and neurotrophic pathways. Specifically, NC increased expression of Bdnf, Irs2, and Pgc-1α, while attenuating aberrant upregulation of Insr, Igf1r, and markers of ageing and AD-related pathology (Sirt1, Gdf15, Arc, Egr1, Cldn5). These findings indicate that NC therapy mitigates behavioural and molecular hallmarks of AD, potentially via restoration of BDNF and insulin receptor-mediated signalling. Full article

Fenofibrate (FF), a lipid-lowering drug, may decrease the risk of cardiovascular diseases in some pathological settings, yet data on its cardiac effects in physiological aging is scarce. To determine FF and age effects on the heart’s morphology and expression of metabolism-related genes, we treated young and old male rats for 30 days with 0.1% or 0.5% FF. FF did not affect serum activities of LDH and creatine kinase in both age groups. Upon FF treatment the structure of the heart muscle did not change in young rats; however, 0.5% FF increased the abundance of collagen fibers in old rats, and lipid accumulation in cardiomyocytes in young and old animals. FF increased immunoreactivity of the hypertrophy marker NPPA that was more pronounced in old than in young rats, while VEGFB immunoreactivity did not change. FF upregulated phospho-AMPK and PGC1α protein levels only in the cardiac muscle of old rats, while in both age groups it mildly increased the expression of selected fatty acid oxidation genes. We conclude that the cardiac muscle response to FF is dose-dependent and influenced by age. The observed negative impact of high-dose FF in the hearts of aged rats underscores the importance of dose optimization in the elderly. Full article