Search Results (815)

The anti-aging gene/protein Klotho (Kl), most present in kidneys, has been well studied in mice (mKl), but not in rats (rKl). This study investigated the renal rKl expression in male and female rats. Sex-related measurement of rKl-controlled electrolytes was performed in plasma/urine samples, as were tests on species differences in renal Kl expression (rats vs. mice). rKl mRNA/protein expression was studied by qRT-PCR/Western-blotting in renal total RNA/cell membranes and its localization by immunofluorescence microscopy. Urine/plasma ions (phosphate/total calcium) and macroelements (phosphorus/calcium) were measured biochemically and by ICP-MS, respectively. In rat kidneys, the rKl mRNA/protein was detected in the cortex, outer and inner stripe but not in the papilla, and was immunolocalized in the basolateral membrane of proximal tubules in the cortex and outer stripe, but not in the intercalating cells of the cortical distal tubules, whereas mKl was observed in the mouse kidney cortex but not the outer stripe. Female-dominant expression of renal rKl, affected by androgen’s inhibitory effect, may have contributed to the sex-related level of urine electrolytes, particularly phosphates. Renal mKl expression was male-dominant. Sex- and species-related differences in renal Kl expression may be relevant for the selection of the sex and/or the model organism in studies addressing aging/mineral homeostasis. Full article

Background: Common variable immunodeficiency is a heterogeneous disorder characterized by defects in antibody production and immune dysregulation, associated with infections and autoimmunity. Although structural and cognitive effects of CVID on the central nervous system have attracted attention in recent years, studies jointly addressing volumetric brain imaging and neurocognitive evaluation remain limited. Materials and Methods: In this retrospective cross-sectional study, 35 patients with common variable immunodeficiency and 40 age- and sex-matched healthy controls were evaluated. Cognitive performance was assessed in all participants using the Montreal Cognitive Assessment. High-resolution T1-weighted brain magnetic resonance imaging scans underwent automated segmentation using the volBrain platform, yielding quantitative volumetric measurements of cortical, subcortical, and cerebellar structures, as well as ventricles and cerebrospinal fluid. Intergroup comparisons were performed using independent t-tests and analysis of variance. Results: MoCA scores were significantly lower in patients with CVID. Volumetric analysis revealed prominent reductions in the volumes of total brain tissue, gray matter, cerebrum, cerebellum, limbic system, thalamus, and basal ganglia. Paralleling these findings, cerebrospinal fluid and lateral ventricle volumes were increased. Additional volume losses were detected in CVID patients with low MoCA scores. In CVID patients with autoimmunity, volume loss affected broader areas. Conclusions: CVID appears to be associated with structural brain changes and cognitive impairments. Chronic inflammation and immune dysregulation may contribute to these neurodegenerative processes. Regular neurocognitive monitoring and further prospective studies are warranted in patients with CVID. Full article

Background: The current biomarker classification system does not fully explain the increased prevalence of both Alzheimer’s disease (AD) and vascular risk factors for AD—such as diabetes and hypertension--among African Americans (AAs) compared to White participants. Research on cognitive aging has traditionally focused on how declines in cortical and hippocampal regions influence cognition. However, tau pathology emerges decades before amyloid pathology, initially appearing in the brainstem, particularly in the locus coeruleus (LC), the primary source of the brain’s norepinephrine (NE). Further, postmortem studies suggest that the loss of LC neurons is a better predictor of AD symptom severity than amyloid-beta/neurofibrillary tangle pathology in any other brain region. Methods: Our decade-long studies in humans using a norepinephrine transporter (NET)-selective radiotracer ([¹¹C]MRB) have demonstrated that LC is uniquely vulnerable to aging and stress. In this retrospective study, regression slopes with age (RSAs) for regional NET availability were compared across groups and tested for statistical significance. Results: In our primary analysis, higher NET availability was observed in AAs (N = 14; 7 males aged 23–49), particularly at younger ages, as compared to White (N = 16; 11 males aged 24–55) participants. Our preliminary data also suggest that the rate of decline in NET availability is faster in AAs, with a potential trend toward a more pronounced effect in AA males as compared to White males (e.g., in the left thalamus, RSA was −3.03%/year [95%CI: −5.80% to 1.19%] for AA males vs. RSA = −0.14 for White males [95%CI: −0.79% to 0.47%]. Additionally, in the right anterior cingulate cortex, RSA was −3.4%/year [95%CI: −4.6% to −1.4%] for AA males, compared to RSA = 0.3%/year [95%CI: 0.04% to 1.03%] for White males). Conclusions: This report reveals that NET availability (measured with [¹¹C]MRB) can serve as a biomarker to index the function of the LC-NE system and that the fast-decline rate of NET in AAs implicates a potential molecular mechanism underlying health disparities observed in the disproportionate AD prevalence. Full article

The objective of the present study was to investigate whether orthodontic treatment alters the morphology and bone mineral density (BMD) distribution of the mandibular condyle in growing adolescent patients. Cone-beam computed tomography (CBCT) images were retrospectively analyzed for 29 patients (10 males and 19 females, aged 12.5 to 17.0 years) treated with full fixed orthodontic appliances. The right and left mandibular condyles were digitally isolated. For the internal control sample, the basal cortical bone (CB) at both mandibular first molar sites was also digitally dissected. A frequency plot of the CBCT gray values, proportional to BMD, was analyzed to calculate the mean and the 5th percentile of low and high gray values (Low₅ and High₅). Morphological changes in the condylar surface were assessed based on temporomandibular joint osteoarthritis (TMJOA) counts. Lateral cephalometric radiographs were used to measure facial morphology parameters and classify skeletal patterns. The cervical vertebral gray values of the same patients were compared. No radiographic signs of TMJ disorder were observed with no significant difference in TMJOA counts between before and after treatment (p = 0.56). The volume, mean and Low₅ gray values of the mandibular condyle, facial morphology parameters, and cervical vertebral gray values significantly increased following orthodontic treatment (p < 0.05). Skeletal Class II patients exhibited greater changes in mean, Low₅, and High₅ mandibular condyle gray values compared to their Class I patients (p < 0.05), whereas cervical vertebral gray values were not significantly influenced by skeletal classification (p > 0.19). The findings suggest that orthodontic treatment, combined with natural patient growth, contributes to nonpathological condylar alterations in adolescent patients. Full article

Brain age has been widely recognized as an important biomarker for monitoring adolescent brain development and assessing dementia risk. However, existing model visualization methods primarily highlight brain regions associated with aging, making it difficult to comprehensively reveal broader brain changes. In this study, we developed a VGGNet-based brain age prediction model and proposed the Softmax-Derived Brain Age Mapping algorithm to simultaneously identify brain regions associated with both youthful and aging features. The resulting saliency maps provide explicit representations of developmental and degenerative processes across different brain regions. Brain Age Map analysis revealed that aging features in the healthy group were primarily confined to the frontal cortex, aligning with findings that the frontal lobe is the earliest region to undergo natural senescence. In contrast, the dementia group exhibited widespread aging across the frontal, temporal, parietal, and occipital lobes, as well as the ventricular regions. These results suggest that the spatial distribution of brain aging can serve as a critical biomarker for distinguishing normal aging trajectories from pathological degeneration. From an application perspective, we further explored the potential of the proposed framework in neurodegenerative diseases. The analysis reveals that dementia patients generally exhibit an advanced brain age, with cortical aging being markedly more pronounced than in age-matched healthy samples. Notably, although dementia cases were not included in the training set, the model was still able to localize abnormalities in relevant brain regions, underscoring its potential value as an assistive tool for early dementia diagnosis. Full article

Background/Objectives: Autism spectrum disorder is associated with executive functioning (EF) challenges, yet the neural correlates of EF challenges in autistic youth remain unclear. This study aimed to examine EF performance and cortical activation in autistic versus non-autistic youth, using functional near-infrared spectroscopy (fNIRS) during a modified Flanker task. Methods: Thirty age-matched (11.6 ± 0.8 years) autistic (N = 15) and non-autistic youth (N = 15) completed congruent and incongruent conditions of a modified Flanker task while cortical activation in prefrontal, parietal, and temporal regions was recorded using fNIRS. The Behavior Rating Inventory of Executive Function (BRIEF) was used to assess general EF impairments. Behavioral data (i.e., Flanker task mean reaction time/accuracy, and reaction time variability) and cortical activation were analyzed using ANCOVAs. Pearson correlations were used to determine the relationship between cortical activation, EF performance, and clinical measures. The significance level was set at p < 0.05, with FDR corrections for multiple comparisons. Results: While mean reaction time and accuracy were comparable across groups, autistic youth exhibited greater reaction time variability (autistic youth = 34.8 ± 10.36; controls = 26.4 ± 1.94, p = 0.02, Hedges’ g = 0.85) and higher BRIEF index scores compared to controls (p_s < 0.001, Hedges’ gs > 1.3; e.g., Global Executive Composite Score for autistic youth = 71.3 ± 3.7; controls = 47.8 ± 2.4), indicative of delayed EF development. During the incongruent condition, compared to non-autistic controls, autistic youth showed lower left inferior parietal lobe (IPL) activation (Mean HbO₂ in autistic youth = −0.02 ± 0.006 mmol.mm; controls = 0.01 ± 0.006 mmol.mm, p_s < 0.001, Hedges’ g = 0.5) and a lack of left-lateralized activation (e.g., left vs. right STS activation, p < 0.001, Hedges’ g = 0.41 in the non-autistic youth). In the ASD group, lower activation in the left STS was associated with lower EF performance (r = −0.28, p = 0.007), whereas greater activation in various right-hemispheric ROIs was associated with better EF performance (r = −0.31 to −0.35, p_s < 0.005), suggesting potential compensatory activation. Conclusions: The findings revealed ASD-specific differences in the neural correlates of EF performance and possible alternative compensatory activation patterns. These potential neural correlates of EF performance highlight the utility of fNIRS-based neural measures to better understand the neural bases of EF differences in autism. Study Registration: This study was approved by the Institutional Review Board (IRB) at the University of Delaware (Protocol #: 1947455) on 4 October 2022. Full article

Background: Transcranial direct current stimulation (tDCS) involves the application of weak electric currents (typically 0.5–2 mA) via scalp electrodes to promote neuroplastic changes that modulate behaviour or cortical activity. Although there have been promising results in eliminating tinnitus or reducing its loudness or severity, there is also a high degree of inter-individual variability. This may be due to anatomical differences and their influence on the resulting electric field. To optimise and personalise tDCS protocols, computational electric field models based on individual clinical imaging may be utilised to give insight into the induced electric field during tDCS and inform more effective protocols for targeted stimulation. To our knowledge, there are currently no standards for current modelling or reviews which detail the optimal parameters for conducting current modelling studies for tDCS. Objectives: The aim of this review is to investigate the methodology of current modelling studies for tDCS so that informed, personalised protocols can be designed by modelling the electric field of the brain during tDCS for tinnitus. By considering the impact of individual anatomical differences on the electric field induced by tDCS, targeted protocols could be developed to reduce tinnitus loudness and severity in a systematic and predictable way. Design: The protocol for this review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) Checklist. Using online databases, records were identified based on a keyword search for records relevant to current modelling for tDCS, including peer-reviewed papers, clinical trials, the grey literature, theses, dissertations, and conference abstracts. Four thousand two hundred and fifty-three records were retrieved from thirteen online databases and include 4186 records from the initial search completed between May and July 2024, and 67 records from an updated search completed in August 2025. A further 596 records were retrieved from Google Scholar (501 from the initial search and 95 from the updated search). One hundred and fourteen records met our criteria for inclusion. Each record was charted by two separate reviewers, with attention to the modelling pipeline and predicted values in peak and range of electric field magnitude. Results: There was a consensus that, despite model parameters and pipelines, there was inter-individual variability in the predicted electric fields. The reviewed records highlighted the impact of individual differences, including age, sex, and anatomical variation, on the predicted electric field during tDCS. Increased age was often associated with age-related brain atrophy and high relative cerebrospinal fluid volume, which was a significant influence on the resulting E-field intensity and distribution. Conclusions: When creating personalised tDCS protocols for tinnitus, the model parameters and sources of variability (i.e., morphology, age, and sex) should be carefully considered to achieve the desired stimulation outcomes, particularly in regard to applied current intensity. Full article

Tourette syndrome (TS), or Tourette’s, is a tic disorder (TD) belonging to a group of neuropsychiatric conditions marked by recurrent motor movements or vocalizations known as tics. TD, including TS, typically begins in childhood between 4 and 18 years of age and affects approximately 3% of children and adolescents. The etiology and pathogenesis of TD are multifactorial, involving genetic, immunologic, psychological, and environmental factors. Evidence suggests that neurotransmitter dysregulation, particularly within the cortical dopaminergic networks of the basal ganglia and limbic system, which support motor control and cognition, may be involved in the development of TD. Nutritional factors may modulate TD through various mechanisms, including effects on neurotransmitter synthesis and metabolism, neurodevelopment, neural architecture, and neuroimmune activity. This review integrates current evidence on the roles of vitamins D, B6, and A, as well as iron, magnesium, zinc, and copper, in TD. For each micronutrient, its physiological and neurobiological functions are discussed, along with possible mechanistic links to TD pathophysiology. Additionally, we summarize the impact of nutrient deficiencies and assess available evidence regarding their potential therapeutic potential role in TD management. Overall, this synthesis highlights how nutritional status may influence TD onset and symptom severity, suggesting that nutrient-based interventions could potentially serve as valuable adjunctive strategies in treatment. Full article

Background/Objectives: Parkinson’s disease (PD) is an adult-onset neurodegenerative disorder whose pathogenesis is still not completely understood. Several lines of evidence suggest that alterations in epigenetic architecture may contribute to the development of this condition. Here, we present a pilot DNA methylation study from peripheral blood in a cohort of Sicilian PD patients and matched controls. Peripheral tissue analysis has previously been shown to reflect molecular and functional profiles relevant to neurological diseases, supporting their validity as a proxy for studying brain-related epigenetic mechanisms. Methods: We analyzed 20 PD patients and 20 healthy controls (19 males and 21 females overall), matched for sex, with an age range of 60–87 years (mean 72.3 years). Peripheral blood DNA was extracted and processed using the Illumina Infinium MethylationEPIC v2.0 BeadChip, which interrogates over 935,000 CpG sites across the genome, including promoters, enhancers, CpG islands, and other regulatory elements. The assay relies on sodium bisulfite conversion of DNA to detect methylation status at single-base resolution. Results: Epigenome-wide association study (EWAS) data allowed for multiple levels of analysis, including immune cell-type deconvolution, estimation of biological age (epigenetic clocks), quantification of stochastic epigenetic mutations (SEMs) as a measure of epigenomic stability, and differential methylation profiling. Immune cell-type inference revealed an increased but not significant proportion of monocytes in PD patients, consistent with previous reports. In contrast, epigenetic clock analysis did not reveal significant differences in biological age acceleration between cases and controls, partially at odds with earlier studies—likely due to the limited sample size. SEMs burden did not differ significantly between groups. Epivariations reveal genes involved in pathways known to be altered in dopaminergic neuron dysfunction and α-synuclein toxicity. Differential methylation analysis, however, yielded 167 CpG sites, of which 55 were located within genes, corresponding to 54 unique loci. Gene Ontology enrichment analysis highlighted significant overrepresentation of pathways with neurological relevance, including regulation of synapse structure and activity, axonogenesis, neuron migration, and synapse organization. Notably, alterations in KIAA0319, a gene involved in neuronal migration, synaptic formation, and cortical development, have previously been associated with Parkinson’s disease at the gene expression level, while methylation changes in FAM50B have been reported in neurotoxic and cognitive contexts; our data suggest, for the first time, a potential epigenetic involvement of both genes in Parkinson’s disease. Conclusions: This pilot study on a Sicilian population provides further evidence that DNA methylation profiling can yield valuable molecular insights into PD. Despite the small sample size, our results confirm previously reported findings and highlight biological pathways relevant to neuronal structure and function that may contribute to disease pathogenesis. These data support the potential of epigenetic profiling of peripheral blood as a tool to advance the understanding of PD and generate hypotheses for future large-scale studies. Full article

Myocardial infarction (MI) and heart failure (HF) are associated with low bone mineral density (BMD). We aimed to investigate whether MI and HF directly cause bone loss using three different experimental models of cardiac injury. Firstly, terminal myocardial infarction was induced in adult wild-type mice by coronary ligation, followed by peripheral quantitative computed tomography (pQCT) and histomorphometric and biochemical analyses at 4 and 9 weeks post-infarction. Secondly, myocardial ischemia–reperfusion injury (I/R) was performed in 4- and 9-month-old rats, followed by bone phenotyping 4 weeks after injury. Finally, transverse aortic constriction (TAC) was performed in adult wild-type mice, double Fgf23/VDR (fibroblast growth factor-23/vitamin D receptor) mutants, and VDR-deficient mice to investigate bone changes in an HF model caused by afterload-induced cardiac hypertrophy, 4 and 6 weeks after TAC. We found unchanged BMD after MI, in both the terminal ischemia model in mice and in the myocardial I/R injury model in young and aged rats. On the other hand, TAC significantly reduced especially cortical BMD in femora. Global knockout of Fgf23 in Fgf23/VDR compound mutants did not rescue the TAC-induced skeletal phenotype. Collectively, our data demonstrate that TAC-induced HF, but not MI, is causing bone loss in mice in an FGF23-independent manner. Full article

Aging profoundly modifies neuronal responses to ischemia. We aimed to define age-dependent features of neuronal metabolism and cell death after ischemic stroke by assessing NeuN, NSE, and Caspase-3 in human cortical neurons and by comparing transcriptional activity within PI3K/Akt/mTOR and PI3K/Akt/FOXO3a pathways across age groups. The aim of this study was to determine age-dependent features of neuronal metabolism and cellular degradation in ischemic stroke based on immunohistochemical assessment of NeuN, NSE, and Caspase-3 markers in human cerebral cortex neurons, as well as to conduct a comparative analysis of gene expression in the PI3K/Akt/mTOR and PI3K/Akt/FOXO3a signaling pathways involved in the regulation of neuronal survival and apoptosis. For the investigation, frontal cortex autopsies from patients with ischemic stroke (n = 154; “young”, “middle” and “elderly”; death ≤7 days post-onset) were examined. Histology (hematoxylin–eosin) and Nissl staining were used for morphology and neuron counts. Multiplex immunofluorescence (NeuN, NSE, Caspase-3) quantified metabolically active and apoptotic neurons, and the percentage of Caspase-3⁺ among NeuN⁺ cells was calculated. qRT-PCR measured PIK3CA, AKT2, MTOR, and FOXO3A expression in the infarct border zone. Based on our results, neuronal density and NeuN/NSE expression declined with aging, and the fraction of Caspase-3⁺ among NeuN⁺ neurons in the penumbra rose (young 42%, middle 82%, elderly 89%). Morphologically “intact” penumbral neurons frequently lacked NeuN/NSE, revealing covert dysfunction. Young brains showed balanced activation of PI3K/Akt/mTOR and PI3K/Akt/FOXO3a, whereas elderly brains exhibited reduced Akt/mTOR activity with FOXO3A predominance, consistent with pro-apoptotic, inflammatory, and dysregulated autophagic signaling. Thus, aging markedly reduces neuronal metabolic activity and increases apoptotic death in the infarct border zone after ischemic stroke. In older patients, there is an almost complete loss of NeuN and NSE expression in penumbral neurons with robust activation of the caspase cascade, whereas younger patients retain a pool of metabolically active neurons. Age-dependent dysregulation of PI3K/Akt signaling—characterized by FOXO3a hyperactivation and mTOR suppression—further promotes apoptosis and dysregulated autophagy. These changes likely underlie the limited efficacy of standard neuroprotection in ischemic stroke and support the need for age-tailored neurotropic therapy aimed at enhancing pro-survival pathways within the infarct border zone. Full article

Background/Objectives: Osteoporosis is highly prevalent and contributes substantially to morbidity and mortality, yet long-term concerns about pharmacologic therapies leave a major treatment gap. Soy isoflavones have been investigated as safer alternatives, but results across trials are inconsistent. A key unresolved issue is the equol-producer phenotype, the gut microbial ability to convert daidzein to S-equol, the most bioactive isoflavone metabolite, which may explain much of this variability. This narrative review synthesizes mechanistic, translational, and clinical evidence to clarify the potential skeletal relevance of S-equol. Methods: Literature was identified through PubMed and Scopus searches (January 2000–October 2025) for experimental, mechanistic, and clinical studies examining S-equol, estrogen receptor β (ERβ), and bone metabolism, with emphasis on equol-producing status, bone strength and bone microarchitecture. Results: S-equol acts as a high-affinity ERβ agonist with antioxidant and anti-inflammatory properties but lacks the carcinogenic or thrombotic risks linked to ERα activation. In estrogen-deficient rodent models, S-equol improves trabecular bone volume by 10–20%, increases trabecular number, and enhances biomechanical strength. These findings align with preclinical evidence demonstrating that S-equol preserves trabecular microarchitecture, enhances bone strength, and reduces bone turnover. A limited number of human trials show reductions in bone resorption by 20% at a daily dose of 10 mg S-equol. In contrast, trials of soy isoflavones in humans have produced inconsistent findings, partly because of substantial variability in equol-producer phenotype among participants and the reliance on dual-energy X-ray absorptiometry, which cannot distinguish trabecular from cortical compartments. Advanced bone imaging and microbiome-informed approaches enable the precise evaluation of S-equol’s skeletal effects on trabecular bone and cortical bone, separately. Conclusions: S-equol represents a promising model for “precision nutrition,” where microbiome, hormonal, and host factors converge with potential to prevent age-related bone fragility. Rigorous trials that integrate microbiome phenotyping and advanced imaging are needed to validate this approach, translate mechanistic promise into clinical benefit, and better define safety. Full article

Brainwave entrainment (BWE) through Binaural Beats (BBs) has been proposed as a non-invasive method to modulate cortical activity by enhancing oscillatory power at specific frequencies. Despite growing interest, empirical evidence regarding the efficacy of BBs remains inconsistent. This study aimed to assess long-term effects of BBs stimulation using a personalized protocol. Eleven healthy university students (7 males, 4 females; mean age 24.8 ± 1.6 years) participated in three EEG acquisition sessions over two weeks, each including Baseline, Stimulation, and Post-Stimulation phases. Personalized audio tracks were created based on each participant’s Individual Alpha Frequency (IAF) and applied daily during a 10-day training period. EEG signals were analysed in time and frequency domains using linear and complexity-based metrics. Multivariate processing combining Principal Component Analysis and K-means clustering revealed high classification accuracy distinguishing Baseline from Stimulation (>81%) and Baseline from Post-Stimulation (>89%) phases, with consistent results across sessions and in pooled data. Statistical significance was confirmed via non-parametric permutation testing. Alpha rhythm analysis showed significant frontal effects (F3, F4), including increased spindle incidence, reduced duration, decreased alpha power, and lowered $\alpha$ exponent via Detrended Fluctuation Analysis. Although the dataset was relatively small, these findings suggest that BBs may modulate brain activity, with sustained effects observable post-stimulation, particularly in frontal regions. Full article

Objective: Gliomas disrupt functional brain networks and impair neurological functions. While left-hemispheric tumors are well-studied because of their impact on language domains, the influence of right-sided gliomas on higher cognitive functions remains less understood. This study aimed to assess pre- and postoperative neurocognitive performance and to link cognitive outcomes with structural findings derived from function-based tractography in patients with right-hemispheric gliomas. Methods: Patients with gliomas were enrolled in this prospective observational study. A structured neurocognitive test battery was administered preoperatively, postoperatively, and at 3-month follow-up. Preoperative cortical mapping using navigated transcranial magnetic stimulation (nTMS) and function-based fiber tracking, based on diffusion tensor imaging (DTI), was performed. Results: Eighteen patients aged 52.7 ± 18.3 years were included. Preoperatively, 88.8% of patients showed impairments in at least one cognitive test, most frequently in the Nine-Hole Peg Test (66.7%), Bells Test task completion time (61.1%), Trail Making Test A and B (TMT-A: 50.0%; TMT-B: 44.4%), and digit symbol substitution test (27.8%). At follow-up, task performance improved on most cognitive tests. Function-based tractography showed that involvement of the superior longitudinal fasciculi I–III (44.4% of cases) was associated with impairments in attention, executive function, visuospatial processing, and processing speed. The involvement of the inferior frontooccipital fasciculus (55.5% of cases) was related to deficits in processing speed, attention, executive function, and episodic memory. Conclusions: Neurocognitive deficits are common in patients with right-hemispheric gliomas even before surgery. Maximal safe resection and sparing of these tracts is associated with cognitive recovery at follow-up. Function-based tractography emphasizes the structural involvement of key association fibers related to these cognitive deficits. Full article

Ultrasound is the primary, non-invasive imaging modality for evaluating renal anatomy and function in both acute and chronic settings. Familiarity with normal kidney morphology, cortical and parenchymal thickness, echogenicity, and Doppler parameters is essential for differentiating normal findings from early manifestations of disease. This review summarizes established reference ranges and anatomical variants from the 1950s to 2025, highlighting differences related to age, sex, body habitus, and ethnicity. Practical emphasis is placed on the interpretation of renal size, cortical thickness, echogenicity, and resistive indices in clinical scenarios such as chronic kidney disease, renovascular hypertension, acute obstruction, and renal transplantation. By integrating sonographic measurements with clinical and laboratory findings, clinicians can achieve timely diagnosis, monitor disease progression, and guide therapeutic decisions while minimizing the need for invasive or radiation-based imaging. Full article