Significant Age-related Changes Research Articles

Dissociation of focal and large-scale inhibitory functions in the older adults: A multimodal MRI study

BackgroundThe decline of inhibitory in cognitive aging is linked to reduced cognitive and mental capacities in older adults. However, this decline often shows inconsistent clinical presentations, suggesting varied impacts on different inhibition-related tasks. Inhibitory control, a multifaceted construct, involves various types of inhibition. Understanding these components is crucial for comprehending how aging affects inhibitory functions. Our research investigates the influences of aging on large-scale and focal-scale inhibitory and examines the relationship with brain markers. MethodsWe examined the impact of aging on inhibitory in 18 younger (20–35 years) and 17 older adults (65–85 years) using focal and large-scale inhibition tasks. The Gabor task assessed focal-scale inhibition, while the Stop Signal Task (SST) evaluated large-scale inhibition. Participants underwent neuropsychological assessments and MRI scans, including magnetic resonance spectroscopy (MRS) and structural and resting fMRI. ResultsOlder adults exhibited a marked decline in inhibitory function, with slower SST responses indicating compromised large-scale inhibition. Conversely, the Gabor task showed no significant age-related changes. MRS findings revealed decreased levels of GABA, glutamate, glutamine, and NAA in the pre-SMA, correlating with observed large-scale inhibition in older adults. Additionally, pre-SMA seed-based functional connectivity analysis showed reduced brain network connections in older adults, potentially contributing to inhibitory control deficits. ConclusionsOur study elucidates the differential effects of aging on inhibitory functions. While large-scale inhibition is more vulnerable to aging, focal-scale inhibition is relatively preserved. These findings highlight the importance of targeted cognitive interventions and underscore the necessity of a multifaceted approach in aging research.

O-033 Molecular insights into the decline in oocyte quality with advanced maternal age: findings from comprehensive single cell -omics analysis of 112 human oocytes

Abstract Study question How does maternal age impact the molecular composition of oocytes during their final meiotic progression? Summary answer Maternal age significantly correlates with proteomic changes during oocyte maturation, particularly in proteostasis and meiosis related proteins, with minimal impact on transcriptome and DNA-methylation patterns. What is known already Oocyte quality declines with maternal age, resulting in diminished developmental competence and higher aneuploidy rates. However, the molecular mechanisms behind this decline in oocyte quality remain elusive. Transcriptomic studies have revealed few differentially expressed genes in advanced maternal age (AMA) oocytes, suggesting that age-related changes in oocyte quality result from a complex interplay of molecular factors, rather than a single cause. However, comprehensive methylation and proteomic data are still lacking. We employed advanced -omics to assess the effect of maternal age on the molecular signature of human oocytes, focusing on DNA-methylation, transcriptome and proteome changes during the final meiotic progression. Study design, size, duration This study included a total of 112 oocytes obtained from young (<35 years, n = 35) and AMA women (>37 years, n = 55), who were recruited in the study from October 2021 to October 2023. Both germinal vesicle (GV, n = 68) and metaphase II (MII, n = 44) oocytes were analysed. Additionally, 19 immature oocytes (GV and metaphase I) from 9 young women were used for validation. Participants/materials, setting, methods Parallel single-cell bisulfite and RNA sequencing was applied to 44 oocytes (26 GV-Young, 6 MII-Young, 8 GV-AMA, 4 MII-AMA) and single-cell proteomics to 68 oocytes (18 GV-Young, 18 MII-Young, 18 GV-AMA, 14 MII-AMA). Additionally, 10 GV and 9 MI oocytes were treated with the proteasome inhibitor MG-312 (0 µM, 10 µM) for 6 hours, followed by rescue in vitro maturation (rIVM) for 36 hours. Chromosomal distribution was assessed by immunocytochemistry. Main results and the role of chance Our analysis revealed no significant changes in DNA methylation patterns in either GV nor MII oocytes associated with AMA. Also, very limited changes were detected in the transcriptome, with transcript levels of only 5 genes in GV oocytes and 7 genes in MII oocytes detected as being significantly changed. In contrast, proteomic analysis, particularly in GV oocytes, revealed significant age-related changes, notably in proteins participating in the proteostasis network (signalosome complex, UCHL1) including chaperones (TRiC-complex, HSP7C, STIP1), and in the cell cycle, including signal transduction factors (1433E, integrins) and cytoskeleton regulators (DYL2, CAPZB, ARHGG) (Rs ≤ |0.5|, p ≤ 0.05). The proteasome complex, which plays a crucial role both in meiosis and the proteostasis network, was found to decline with age; changes were evident in several subunits of the complex (e.g., PRS8, PRS6A, and PRS10; Rs ≤ -0.56, p ≤ 0.05). Compared to controls, treatment of immature oocytes with the proteasome inhibitor MG-132 resulted in either maturation failure or chromosome mislocalization in metaphase plate, further validating the essential role of the proteasome during oocyte maturation. In MII oocytes, 7 proteins showed alterations with age, including the oocyte-specific marker DDX4, which significantly declined in abundance (Rs =-0.6, p ≤ 0.05). Limitations, reasons for caution Unlike GVs that were collected fresh, MII oocytes underwent vitrification and warming before being included in the study due to clinical protocols. These procedures may have unknown effects on the transcriptome and proteome. Wider implications of the findings Our findings suggest that age primarily affects oocyte quality at the post-transcriptional level, potentially through meiosis dysregulation and proteostasis disruption. We also demonstrate the proteasome's vital role in oocyte maturation, suggesting that targeting the proteasome complex may improve oocyte quality in AMA women. Trial registration number Not applicable

Age-related changes of dopamine D1 and D2 receptors expression in parvalbumin-positive cells of the orbitofrontal and prelimbic cortices of mice.

Dopamine (DA) plays a pivotal role in reward processing, cognitive functions, and emotional regulation. The prefrontal cortex (PFC) is a critical brain region for these processes. Parvalbumin-positive (PV+) neurons are one of the major classes of inhibitory GABAergic neurons in the cortex, they modulate the activity of neighboring neurons, influencing various brain functions. While DA receptor expression exhibits age-related changes, the age-related changes of these receptors in PV+ neurons, especially in the PFC, remain unclear. To address this, we investigated the expression of DA D1 (D1R) and D2 (D2R) receptors in PV+ neurons within the orbitofrontal (OFC) and prelimbic (PrL) cortices at different postnatal ages (P28, P42, P56, and P365). We found that the expression of D1R and D2R in PV+ neurons showed both age- and region-related changes. PV+ neurons in the OFC expressed a higher abundance of D1 than those in the PrL, and those neurons in the OFC also showed higher co-expression of D1R and D2R than those in the PrL. In the OFC and PrL, D1R in PV+ neurons increased from P28 and reached a plateau at P42, then receded to express at P365. Meanwhile, D2R did not show significant age-related changes between the two regions except at P56. These results showed dopamine receptors in the prefrontal cortex exhibit age- and region-specific changes, which may contribute to the difference of these brain regions in reward-related brain functions.

Normal spinopelvic parameters and correlation analysis in 217 asymptomatic children

BackgroundUnderstanding spinal sagittal balance is crucial for assessing and treating spinal deformities in pediatric populations.ObjectiveThe aim of the present observational study is to examine the parameters of sagittal alignment of the regional spine and spinopelvic region in asymptomatic pediatric populations and the characteristics of these parameters with age and sex.MethodsWe enrolled 217 participants, consisting of 112 males (51.6%) and 105 females (48.4%), aged between 4 and 15 years, with an average age of 12.19 years. Pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, T1 slope, C7 slope, cervical sagittal vertical axis, and C2–7 Cobb angle were measured. Three spine surgeons conducted radiographic measurements utilizing the PACS software. The measurement reliability was assessed through ICCs.ResultsOur results show significant age-related changes in pelvic tilt and cervical sagittal vertical axis, with notable gender differences in pelvic tilt, lumbar lordosis, and thoracic kyphosis. Girls have larger PT, boys have larger cSVA. PI, PT, and cSVA also differ among different age groups. Correlation analysis shows that a series of relationships that align with adult population patterns between pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, and thoracic kyphosis.ConclusionSignificant variations in PT and cSVA across diverse age cohorts highlights notable disparities in the distribution of PT and cSVA values within the pediatric population. Gender-based differences in PT, LL, and TK and correlation in spinopelvic parameter could enhances our understanding of compensatory mechanisms.

Assessment of Age-related Histopathological Changes Occurring in the Lacrimal Gland of Aging Wistar Rats

Purpose. Wistar rats are often used in ophthalmological studies and in testing substances having therapeutic effects. The condition of the eyes of these animals, as well as other mammals, including humans, in the normal state, pathology, and aging, depends on the work of the lacrimal glands. The aim of this study was to develop convenient approaches for determining age-dependent histopathological changes in the exorbital lacrimal glands (ELGs) of aging rats.Material and methods. Isolated ELGs obtained from Wistar rats aged of 8 and 11 months served as a material of the study. Changes in the structure of ELGs were evaluated using methods of computer analysis of morphological patterns and quantitative data processing.Results. The functioning and state of the ELGs are reflected in their dramatic structural changes and progressive inflammation. Our study proposes a simple way to assess the state of ELGs in aging rats using methods of morphology and computer programs. Using the proposed approach, it was shown that in the period from 8 to 11 months of postnatal development, significant age-related changes occur in aging rats. Changes manifest in the progress of parenchymal degeneration and progressive infiltration of the tissue by inflammatory cells.Conclusions. The proposed method of ELG state’s evaluation can be used in ophthalmological studies, and in particular, when studying the development of “dry eye” syndrome and testing the means of its therapy.

Changes in Paraoxonase, β-Glucosidase, and Carbonic Anhydrase Enzymes Related to Age and Scopolamine-Induced Memory Impairment in Rats

This study aimed to investigate the changes in Paraoxonase (PON), Carbonic Anhydrase (CA), and β-glucosidase levels of different aged rats and scopolamine-induced memory impairment rats. This study used young, adult, and middle-aged male Wistar Albino rats. Scopolamine was administered as a single dose/multiple doses and a Morris water maze (MWM) was used for spatial learning testing in rats. Enzyme-linked immunosorbent assays (ELISAs) were used to determine serum and liver PON and β-glucosidase levels. The CA enzyme activity was assayed following the hydration of CO2. As a result of the comparison of age-related and scopolamine-related changes in PON and β-glucosidase levels in liver and serum samples, no significant age-related and scopolamine-effective changes were observed in serum, while liver PON and liver β-glucosidase levels were found to change significantly. CA activity studies, on the other hand, showed that adults have the lowest CA activity compared to young and middle-aged groups and scopolamine inhibited CA activity in vivo. We found that adult rats modeled with memory impairment had statistically lower levels of liver PON and liver β-glucosidase. CA activity was also found to be significantly reduced. β-glucosidase and CA should be further investigated in terms of neurodegenerative disease risk factors, just like PON, whose importance has been determined by numerous studies in the literature.

Characteristics of Eyes With CRB1-Associated EOSRD/LCA: Age-Related Changes

PurposeTo evaluate ocular and retinal features of CRB1-associated early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) for age-related changes. DesignRetrospective cohort study. MethodsSixteen pediatric patients with biallelic CRB1 EOSRD/LCA who had been followed for up to 18 years were reviewed. Results of comprehensive ophthalmic examinations—including visual acuity, refractive error, dark-adapted visual threshold, Goldmann perimetry, and macular optical coherence tomography (OCT)—were analyzed for significant age-related changes using mixed-effects models. ResultsVisual acuity dark-adapted visual sensitivity, and area of seeing visual field (all subnormal from the earliest ages recorded) declined with increasing age. Hyperopia was stable through childhood and adolescence. In CRB1 EOSRD/LCA, OCT extrafoveal inner and outer laminar thicknesses exceeded those in controls but varied little with age, and foveal metrics (depth, breadth, thickness at rim) differed significantly from those in controls, but variations in foveal metrics were not associated with declines in acuity. ConclusionsFrom the youngest ages, retinal and visual function is significantly subnormal and becomes progressively compromised. A goal of future therapies should be intervention at young ages, when there is more function to be rescued.

The aging trajectories of brain functional hierarchy and its impact on cognition across the adult lifespan.

The hierarchical network architecture of the human brain, pivotal to cognition and behavior, can be explored via gradient analysis using restingstate functional MRI data. Although it has been employed to understand brain development and disorders, the impact of aging on this hierarchical architecture and its link to cognitive decline remains elusive. This study utilized resting-state functional MRI data from 350 healthy adults (aged 20-85) to investigate the functional hierarchical network using connectome gradient analysis with a cross-age sliding window approach. Gradient-related metrics were estimated and correlated with age to evaluate trajectory of gradient changes across lifespan. The principal gradient (unimodal-to-transmodal) demonstrated a significant non-linear relationship with age, whereas the secondary gradient (visual-to-somatomotor) showed a simple linear decreasing pattern. Among the principal gradient, significant age-related changes were observed in the somatomotor, dorsal attention, limbic and default mode networks. The changes in the gradient scores of both the somatomotor and frontal-parietal networks were associated with greater working memory and visuospatial ability. Gender differences were found in global gradient metrics and gradient scores of somatomotor and default mode networks in the principal gradient, with no interaction with age effect. Our study delves into the aging trajectories of functional connectome gradient and its cognitive impact across the adult lifespan, providing insights for future research into the biological underpinnings of brain function and pathological models of atypical aging processes.

Topographical Features of Pediatric Electroencephalography during High Initial Concentration Sevoflurane for Inhalational Induction of Anesthesia.

High-density electroencephalographic (EEG) monitoring remains underutilized in clinical anesthesia, despite its obvious utility in unraveling the profound physiologic impact of these agents on central nervous system functioning. In school-aged children, the routine practice of rapid induction with high concentrations of inspiratory sevoflurane is commonplace, given its favorable efficacy and tolerance profile. However, few studies investigate topographic EEG during the critical timepoint coinciding with loss of responsiveness-a key moment for anesthesiologists in their everyday practice. The authors hypothesized that high initial sevoflurane inhalation would better precipitate changes in brain regions due to inhomogeneities in maturation across three different age groups compared with gradual stepwise paradigms utilized by other investigators. Knowledge of these changes may inform strategies for agent titration in everyday clinical settings. A total of 37 healthy children aged 5 to 10 yr underwent induction with 4% or greater sevoflurane in high-flow oxygen. Perturbations in anesthetic state were investigated in 23 of these children using 64-channel EEG with the Hjorth Laplacian referencing scheme. Topographical maps illustrated absolute, relative, and total band power across three age groups: 5 to 6 yr (n = 7), 7 to 8 yr (n = 8), and 9 to 10 yr (n = 8). Spectral analysis revealed a large shift in total power driven by increased delta oscillations. Well-described topographic patterns of anesthesia, e.g., frontal predominance, paradoxical beta excitation, and increased slow activity, were evident in the topographic maps. However, there were no statistically significant age-related changes in spectral power observed in a midline electrode subset between the groups when responsiveness was lost compared to the resting state. High initial concentration sevoflurane induction causes large-scale topographic effects on the pediatric EEG. Within the minute after unresponsiveness, this dosage may perturb EEG activity in children to an extent where age-related differences are not discernible.

Age-related changes in geometry and transparency of human crystalline lens revealed by optical signal discontinuity zones in swept-source OCT images

BackgroundThe shape and microstructure of the human crystalline lens alter with ageing, and this has an effect on the optical properties of the eye. The aim of this study was to characterise the age-related differences in the morphology and transparency of the eye lenses of healthy subjects through the optical signal discontinuity (OSD) zones in optical coherence tomography (OCT) images. We also investigated the association of those changes with the optical quality of the eye and visual function.MethodsOCT images of the anterior segment of 49 eyes of subjects (9–78 years) were acquired, and the OSD zones (nucleus, C1–C4 cortical zones) were identified. Central thickness, curvature and optical density were measured. The eye’s optical quality was evaluated by the objective scatter index (OSI). Contrast sensitivity and visual acuity tests were performed. The correlation between extracted parameters and age was assessed.ResultsThe increase in lens thickness with age was dominated by the thickening of the cortical zone C3 (0.0146 mm/year). The curvature radii of the anterior lens surface and both anterior and posterior nucleo-cortical interfaces decreased with age (− 0.053 mm/year, − 0.013 mm/year and − 0.006 mm/year, respectively), and no change was observed for the posterior lens radius. OCT-based densitometry revealed significant correlations with age for all zones except for C1β, and the highest increase in density was in the C2–C4 zones (R = 0.45, 0.74, 0.56, respectively, P < 0.001). Increase in OSI was associated with the degradation of visual function.ConclusionsOCT enables the identification of OSD zones of the crystalline lens. The most significant age-related changes occur in the C3 zone as it thickens with age at a faster rate and becomes more opaque than other OSD zones. The changes are associated with optical quality deterioration and reduction of visual performance. These findings contribute to a better understanding of the structure–function relationship of the ageing lens and offer insights into both pathological and aging alterations.

Seasonal changes in secretory immunity indices in saliva in indigenous and alien inhabitants of the Yakutia Arctic zone

Introduction. The combination of extreme climate with intensive migration processes creates favourable conditions for the spread of infectious diseases in the Arctic zone of the Russian Federation. &#x0D; The purpose of the study: comparative analysis of immunity indicators in saliva samples of indigenous and alien residents of Yakutia Arctic zone, taking into account the influence of seasonal factors. &#x0D; Materials and methods. Samples of mixed saliva of indigenous (n=212) and alien (n=120) male residents from Chokurdakh and Tiksi settlements were taken in 4 batches corresponding to the seasonal transition from summer to early winter. Levels of secretory IgA (sIgA) and cytokines IL-1ß, IL-8 and IL-6 in saliva were determined by ELISA. Main Effects ANOVA was used for the data analysis. &#x0D; Results. No significant age-related changes of the indicators were found. During the transition from summer to winter, there was a decrease in sIgA, IL-1ß, and IL-8 levels in saliva of the examined persons (p from 0.001 to 1.6•10–7). Rate of seasonal changes did not differ between indigenous and alien inhabitants. IL-6 level in saliva of Chokurdakh residents (200 km from the sea) was higher (F(1,139)=9,202; p=0.003) and sIgA level was lower (F(1,324)=3,560; p=0.060) than corresponding levels in residents of coastal settlement Tiksi. Comparison of the body mass indices (medians 24.3 in Chokurdakh and 26.2 in Tiksi, p=0.0005) confirms that it may be the result of inequality in physical activity of residents due to almost 2-fold increase in wind speed and precipitation in Tiksi. &#x0D; Limitations. Monitoring period till the beginning of winter, and not later, could predetermine the absence of the expected differences between indigenous (evolutionarily adapted) and alien residents. &#x0D; Conclusion. Evaluation of immunity indicators in saliva samples is a simple and informative approach to study mechanisms of human adaptation to extreme climatic conditions.

Multi-omics analysis reveals substantial linkages between the oral-gut microbiomes and inflamm-aging molecules in elderly pigs.

The accelerated aging of the global population has emerged as a critical public health concern, with increasing recognition of the influential role played by the microbiome in shaping host well-being. Nonetheless, there remains a dearth of understanding regarding the functional alterations occurring within the microbiota and their intricate interactions with metabolic pathways across various stages of aging. This study employed a comprehensive metagenomic analysis encompassing saliva and stool samples obtained from 45 pigs representing three distinct age groups, alongside serum metabolomics and lipidomics profiling. Our findings unveiled discernible modifications in the gut and oral microbiomes, serum metabolome, and lipidome at each age stage. Specifically, we identified 87 microbial species in stool samples and 68 in saliva samples that demonstrated significant age-related changes. Notably, 13 species in stool, including Clostridiales bacterium, Lactobacillus johnsonii, and Oscillibacter spp., exhibited age-dependent alterations, while 15 salivary species, such as Corynebacterium xerosis, Staphylococcus sciuri, and Prevotella intermedia, displayed an increase with senescence, accompanied by a notable enrichment of pathogenic organisms. Concomitant with these gut-oral microbiota changes were functional modifications observed in pathways such as cell growth and death (necroptosis), bacterial infection disease, and aging (longevity regulating pathway) throughout the aging process. Moreover, our metabolomics and lipidomics analyses unveiled the accumulation of inflammatory metabolites or the depletion of beneficial metabolites and lipids as aging progressed. Furthermore, we unraveled a complex interplay linking the oral-gut microbiota with serum metabolites and lipids. Collectively, our findings illuminate novel insights into the potential contributions of the oral-gut microbiome and systemic circulating metabolites and lipids to host lifespan and healthy aging.

Long-term survival of LGR5 expressing supporting cells after severe ototoxic trauma in the adult mouse cochlea.

The leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is a tissue resident stem cell marker, which it is expressed in supporting cells (SCs) in the organ of Corti in the mammalian inner ear. These LGR5+ SCs can be used as an endogenous source of progenitor cells for regeneration of hair cells (HCs) to treat hearing loss and deafness. We have recently reported that LGR5+ SCs survive 1 week after ototoxic trauma. Here, we evaluated Lgr5 expression in the adult cochlea and long-term survival of LGR5+ SCs following severe hearing loss. Lgr5GFP transgenic mice and wild type mice aged postnatal day 30 (P30) and P200 were used. P30 animals were deafened with a single dose of furosemide and kanamycin. Seven and 28 days after deafening, auditory brainstem responses (ABRs) were recorded. Cochleas were harvested to characterize mature HCs and LGR5+ SCs by immunofluorescence microscopy and quantitative reverse transcription PCR (q-RT-PCR). There were no significant age-related changes in Lgr5 expression when comparing normal-hearing (NH) mice aged P200 with P30. Seven and 28 days after ototoxic trauma, there was severe outer HC loss and LGR5 was expressed in the third row of Deiters' cells and in inner pillar cells. Seven days after induction of ototoxic trauma there was an up-regulation of the mRNA expression of Lgr5 compared to the NH condition; 28 days after ototoxic trauma Lgr5 expression was similar to NH levels. The presence of LGR5+ SCs in the adult mouse cochlea, which persists after severe HC loss, suggests potential regenerative capacity of endogenous cochlear progenitor cells in adulthood. To our knowledge, this is the first study showing not only long-term survival of LGR5+ SCs in the normal and ototoxically damaged cochlea, but also increased Lgr5 expression in the adult mouse cochlea after deafening, suggesting long-term availability of potential target cells for future regenerative therapies.

Effects of aminophylline therapy on urine output and kidney function in children with acute kidney injury

BackgroundAcute kidney injury (AKI) is a frequent complication of children admitted to the paediatric intensive care unit. One key management modality of AKI is the use of diuretics to reduce fluid overload. Aminophylline, a drug that is well known for its use in the treatment of bronchial asthma, is also purported to have diuretic effects on the kidneys. This retrospective cohort study assesses the effect of aminophylline in critically ill children with AKI.MethodsA retrospective chart review of children admitted to the paediatric intensive care unit of the Red Cross War Memorial Children’s Hospital (RCWMCH) with AKI who received aminophylline (from 2012 to June 2018) was carried out. Data captured and analyzed included demographics, underlying disease conditions, medications, urine output, fluid balance, and kidney function.ResultsData from thirty-four children were analyzed. Urine output increased from a median of 0.4 mls/kg/hr [IQR: 0.1, 1.1] at six hours prior to aminophylline administration to 0.6 mls/kg/hr [IQR: 0.2, 1.9] at six hours and 1.6 mls/kg/hr [IQR:0.2, 4.2] at twenty-four hours post aminophylline therapy. The median urine output significantly varied across the age groups over the 24-h time period post-aminophylline, with the most response in the neonates. There was no significant change in serum creatinine levels six hours post-aminophylline administration [109(IQR: 77, 227)—125.5(IQR: 82, 200) micromole/l] P-value = 0.135. However, there were significant age-related changes in creatinine levels at six hours post-aminophylline therapy.ConclusionsAminophylline increases urine output in critically ill children with AKI.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

EEG Analysis of the Functional State of the Brain in 5- to 7-Year-Old Children

The study is aimed at assessing individual and age-related features of the functional state of various parts of the brain and the patterns of their ontogenetic changes based on the structural analysis of resting-state electroencephalogram (EEG) patterns in 5- to 7-year-old children. The study involved 266 children, who were divided into different age groups: Group 1–5 years old (mean age 4.98 ± 0.33), Group 2–6 years old (mean age 6.03 ± 0.35), and Group 3–7 years old (mean age 6.85 ± 0.22). Alpha-rhythm parameters recorded mainly in the occipital areas may serve as an indicator for the functional maturation of the brain. Significant age-related changes in the alpha-rhythm parameters have been revealed. The presence of a regular alpha-rhythm with a frequency of 8 to 10 Hz increases from 5 to 7 years of age. The occurrence of the alpha-rhythm of reduced frequency significantly decreases by the age of 7 years, and the occurrence of the polyrhythmic alpha-rhythm – by the age of 6 years. These changes are caused both by complications of the structural and functional organization of the cerebral cortex at the cellular level, which occur throughout the studied age period, and the improvement of its relationships with subcortical structures. A decrease in the occurrence of high-amplitude alpha-range electrical activity (EA) with signs of hypersynchrony in the caudal regions may indicate the maturation of the system of nonspecific activation of the brainstem reticular formation from 5 to 7 years of age. Age dynamics is also manifested in a significant decrease in the EEG occurrence of theta-range EA, and its zonal distribution in 5- to 7-year-old children aged. Such changes specify the process of progressive formation of functional connections between individual areas of the cortex, as well as the cortex and subcortical structures, in particular thalamo-cortical ones. The occurrence of alpha-range EA (less than 5.0%) and beta-range EA (about 13.0%) arranged topographically in the anterior cortex did not differ significantly with age. However, generalized EEG activity in the form of different frequency range waves, which characterizes the functional state of predominantly hypothalamic structures, occurs reliably more often in 7-year-old children rather than in 5-year-old children. Such dynamics is presumably associated with an increased reactivity of the hypothalamic-pituitary system in response to adaptive stresses caused by the transition to systematic learning and can be considered as a distinctive feature of this age period. Due to great restructuring of the brain functioning, all its structures become especially sensitive to high intellectual and emotional stress, which is characteristic of preschool children nowadays. The novelty of this study is highlighted by the identification of patterns, structure and nature of EA changes in 5- to 7-year-old normotypical children’s brain to assess the functional state of the cortex and regulatory brain systems. The research results based on a large sample of children, growing up in modern social and cultural conditions, would provide guidance for the formation of age standards.

Immunological features of ESRD patients undergoing hemodialysis of various ages.

To investigate the immunological characteristics of hemodialysis (HD) patients with end-stage renal disease (ESRD) of various ages, and the impact of age-related immune alterations on these patients, with a focus on peripheral T cells. From September 2016 to September 2019, HD patients were enrolled and followed prospectively for 3years. Patients were divided into three groups based on their ages: < 45, 45 to 64, and ≥ 65. The distribution of T cell subsets in different age groups was investigated and compared. The effects of altered T cell subsets on overall survival were also investigated. A total of 371 HD patients were enrolled. The reduced number of naive CD8+ T cells (P < 0.001) and increased number of EMRA CD8+ T cells (P = 0.024) were independently associated with theadvanced age among all T cell subsets studied. Patient survival may be affected by numerical changes in naive CD8+ T cells. However, when HD patients were < 45 or ≥ 65years, the reduction had no significant impacton survival. Only in HD patients aged 45 to 64years, the number of naïve CD8+ T cells found to be insufficient but not deficient, identified as an independent predictor of poor survival. The most significant age-related immune change in HD patients was a decrease in peripheral naive CD8+ T cells, which was an independent predictor of 3-year overall survival in HD patients aged 45 ~ 64years.

Microstructural and Metabolic Changes in Normal Aging Human Brain Studied with Combined Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging

PurposeThis study aimed to detect age-related brain metabolic and microstructural changes in healthy human brains by the use of whole-brain proton magnetic resonance spectroscopic imaging (1H‑MRSI) and quantitative MR imaging (qMRI).MethodsIn this study, 60 healthy participants with evenly distributed ages (between 21 and 69 years) and sex underwent MRI examinations at 3T including whole-brain 1H‑MRSI. The concentrations of the metabolites N‑acetylaspartate (NAA), choline-containing compounds (Cho), total creatine and phosphocreatine (tCr), glutamine and glutamate (Glx), and myo-inositol (mI), as well as the brain relaxation times T2, T2’ and T1 were measured in 12 regions of interest (ROI) in each hemisphere. Correlations between measured parameters and age were estimated with linear regression analysis and Pearsonʼs correlation test.ResultsSignificant age-related changes of brain regional metabolite concentrations and tissue relaxation times were found: NAA decreased in eight of twelve ROIs, Cho increased in three ROIs, tCr in four ROIs, and mI in three ROIs. Glx displayed a significant decrease in one ROI and an increase in another ROI. T1 increased in four ROIs and T2 in one ROI, while T2’ decreased in two ROIs. A negative correlation of tCr concentrations with T2’ relaxation time was found in one ROI as well as the positive correlations of age-related T1 relaxation time with concentrations of tCr, mI, Glx and Cho in another ROI.ConclusionNormal aging in human brain is associated with coexistent brain regional metabolic alterations and microstructural changes, which may be related to age-related decline in cognitive, affective and psychomotor domains of life in the older population.

Impact of Long-Term Shaolin Zen Meditation on Emotional Processing in Aging: A Visual ERP Study.

The aging process is always accompanied by a decline in cognitive and emotional functions. Although previous studies have identified the positive effects of different meditative practices on emotional and cognitive functions, few studies have investigated the most primitive Chinese meditation-Shaolin Zen meditation. In particular, data are extremely limited regarding the brain mechanism of the effects of Shaolin Zen meditation on cognitive and emotional functions during aging. The current study aimed to explore the effects of long-term Shaolin Zen meditation practice on event-related potentials (ERPs) during facial emotion recognition in aging. ERPs were recorded from 16 monks with long-term meditation experience and 20 controls without meditation experience. The significant age-related degenerative changes in the early ERP components did not present in the meditators but only in the controls without meditation experience. Additionally, we found no group differences in the late P3 component. These findings suggest that long-term Shaolin Zen meditation practice can counteract the age-related cognitive decline in the "down-top" automatic processing of emotional stimuli.

Changes of cortical gray matter volume during development: a Human Connectome Project study.

We assessed changes in gray matter volume of 35 cerebrocortical regions in a large sample of participants in the Human Connectome Project-Development (n = 649, 6-21 yr old, 299 males and 350 females). The same protocol for MRI data acquisition and processing was used for all brains. Volumes of individual areas were adjusted for estimated total intracranial volume and linearly regressed against age. We found changes of volume with age that were distinct among areas and consistent between sexes, as follows: 1) the overall cortical volume decreased significantly with age; 2) the volumes of 30/35 areas also decreased significantly with age; 3) the volumes of the hippocampal cortex (hippocampus, parahippocampal, and entorhinal) and that of pericalcarine cortex did not show significant age-related changes; and 4) the volume of the temporal pole increased significantly with age. The rates of volume reduction with age did not differ significantly between the two sexes, except for areas of the parietal lobe where males showed statistically significantly higher volume reduction with age than females. These results, obtained from a large sample of male and female participants, and acquired and processed in the same way, confirm previous findings, offer new insights into region-specific age-related changes in cortical brain volume, and are discussed in the context of the hypothesis that reduction in cortical volume may be partly due to a background, low-grade chronic neuroinflammation inflicted by common viruses residing latently in the brain, notably viruses of the human herpes family.NEW & NOTEWORTHY We report mixed effects of age on cortical gray matter volume during development in a large sample of 649 participants studied in an identical manner (6-21 yr old, 299 males, 350 females). Volumes of 30/35 cortical areas decreased with age, temporal pole increased, and pericalcarine and hippocampal cortex (hippocampus, parahippocampal, and entorhinal) did not change. These findings were very similar in both sexes and provide a solid base for assessing region-specific cortical changes during development.

Empagliflozin improves kidney senescence induced by D-galactose by reducing sirt1-mediated oxidative stress.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have received widespread attention because of their significant protective effects on the kidney. Previous studies have shown that Sirt1, as which is an antiaging protein, is closely related to the maintenance of redox homeostasis. The goal of this study was to determine whether empagliflozin could ameliorate D-galactose-induced renal senescence in mice, and examine the possible mechanisms of Sirt1.We constructed a rapid ageing model in mice by administering D-galactose. An ageing model was constructed by treating cells with high glucose. Treadmill and Y-maze tests were used to assess exercise tolerance and learning memory ability. Pathologically stained sections were used to assess kidney injury. Tissue and cell senescence were evaluated by senescence-associated β-galactosidase staining. The expression levels of P16, SOD1, SOD2 and Sirt1 were detected by immunoblotting.D-gal-treated mice exhibited significant age-related changes, as measured by behavioural tests and ageing marker protein levels. empagliflozin alleviated these ageing manifestations. In addition, Sirt1, SOD1 and SOD2 levels were downregulated in model mice and upregulated by empagliflozin treatment. Empagliflozin had similar protective effects at the cellular level, and these effects were reduced by the Sirt1 inhibitor.Empagliflozin has an antiaging effect, which may be related to reducing Sirt1-mediated oxidative stress.