Significant Age-related Increase Research Articles

Using a Cross-Sectional Analysis of Age-Related Variations in Anthropometric Indices and their Association with Cardiometabolic Health in Adult Men

Background. Age-related changes in anthropometric indices and their association with cardiometabolic health markers are crucial for understanding health risks in adult men. Objectives. The study aimed to assess age-related variations in anthropometric indices and their correlation with health markers, highlighting potential cardiometabolic health risks in adult men. Materials and methods. A total of 200 men, aged 26 to 50 years, from Delhi-National Capital Region (NCR), India, were sampled using a multistage random sampling technique and divided into 5 age groups, each including 40 individuals. This study examined variations in body measurements such as the hip circumference (HC), waist circumference (WC), body mass index (BMI), and neck circumference (NC) across different age groups, as well as their relationship to health markers like HbA1c and lipid profile. Anthropometric measurements were taken in a standardized environment, and blood samples were taken under fasting conditions for lipid profile and HbA1c measurement. With SPSS software, descriptive statistics, a one-way ANOVA, and the Pearson correlation coefficients were used to analyze the data. Results. Significant age-related differences were found in NC and WC, with NC increasing from 39.61 ± 2.53 cm to 41.20 ± 2.63 cm and WC rising from 89.68 ± 12.08 cm to 98.80 ± 9.90 cm, indicating a trend toward central obesity. BMI and HC showed no considerable variation across age groups. A one-way ANOVA revealed significant differences in NC (F = 3.586, p = 0.008) and WC (F = 6.020, p = 0.005). Pearson’s correlations indicated that NC, BMI, and WC were positively correlated with triglycerides, LDL, and VLDL levels (p < 0.05), while no notable correlations were observed for HbA1c. Conclusions. The study underscores the existence of significant age-related increases in NC and WC, suggesting heightened risks of abdominal obesity and cardiometabolic health issues in older men. Monitoring these anthropometric indices is vital for the early detection of health risks in adult males.

Age-induced changes in skeletal muscle mitochondrial DNA synthesis, quantity, and quality in genetically unique rats

AbstractMitochondrial genomic integrity is a key element of physiological processes and health. Changes in the half-life of the mitochondrial genome are implicated in the generation and accumulation of age-induced mitochondrial DNA (mtDNA) mutations, which are implicated in skeletal muscle aging and sarcopenia. There are conflicting data on the half-life of mtDNA, and there is limited information on how aging affects half-life in skeletal muscle. We hypothesized that skeletal muscle mtDNA synthesis rates would decrease with age in both female and male rats concomitant with changes in mtDNA integrity reflected in mtDNA copy number and mutation frequency. We measured mitochondrial genome half-life using stable isotope labeling over a period of 14 days and assessed mtDNA copy number and deletion mutation frequency using digital PCR in the quadriceps muscle of 9-month-old and 26-month-old male and female OKC-HET rats. We found a significant age-related increase in mtDNA half-life, from 132 days at 9 months to 216 days at 26 months of age in OKC-HET quadriceps. Concomitant with the increase in mtDNA half-life, we found an age-related increase in mtDNA deletion mutation frequency in both male and female rats. Notably, 26-month-old female rats had a lower mutation frequency than male rats, and there were no changes in mtDNA copy number with sex, age, or mitochondrial genotype. These data reveal several key findings: (1) mtDNA turnover in rat skeletal muscle decreases with age, (2) mtDNA half-lives in skeletal muscle are approximately an order of magnitude longer than what is reported for other tissues, and (3) muscle mtDNA turnover differs significantly from the turnover of other mitochondrial macromolecules including components of the mitochondrial nucleoid. These findings provide insight into the factors driving age-induced mtDNA mutation accumulation, which contribute to losses of mitochondrial genomic integrity and may play a role in skeletal muscle dysfunction.

The d3GHR carrier epigenome in Druze clan longevity

The Druze are a distinct group known for their close community, traditions, and consanguineous marriages, dating back to the eleventh century. This practice has led to unique genetic variations, impacting both pathology and gene-associated phenotypes. Some Druze clans, particularly those with exceptional long-lived family heads (ELLI), attracted attention. Given that the bulk of these ELLI were men, the d3GHR polymorphism was the first obvious possibility. Among the 73 clan members, 8.2% carried the d3GHR isoform, with nearly 11% being males. There was a significant age-related increase (p = 0.04) in this isoform among males, leading to examination of potential environmental mediators affecting gene regulation among these carriers during life (namely epigenetic). We focused on DNA methylation due to its crucial role in gene regulation, development, and disease progression. We analyzed DNA samples from 14 clan members with different GHR genotypes, finding a significant (p < 0.05) negative correlation between DNA methylation levels and age. Employing a biological age clock, we observed a significant + 4.229 years favoring the d3GHR group over the WT and heterozygous groups. In conclusion, this study highlights the advantage of d3GHR carriers among this unique Druze clan and underscores the importance of genotype-environment interaction in epigenetic regulation and its impact on health.

Plasma C-terminal agrin fragment concentrations across adulthood: Reference values and associations with skeletal muscle health.

Increasing interest surrounds the utility of blood-based biomarkers for diagnosing sarcopenia. C-terminal agrin fragment (CAF), a marker of neuromuscular junction stability, is amongst the most promising candidates; however, a dearth of reference data impedes the incorporation of its use in public health settings. This study aimed to establish reference values for plasma CAF concentrations across adulthood in a large, well-characterized cohort of healthy adults; and comprehensively examine the association between plasma CAF levels and skeletal muscle health. One thousand people aged between 18 and 87years took part in this study (mean age=50.4years; 51% females). Body composition and muscle strength were examined using DXA and hand dynamometry. Plasma CAF concentrations were measured, in duplicate, using commercially available ELISA kits. Sarcopenia and individual sarcopenia signatures [low skeletal muscle index (SMI) only/low grip strength only] were classified using the EWGSOP2 algorithm. Detailed reference CAF values, according to sex and age, are presented. A significant but modest age-related increase in plasma CAF concentration was observed (P=0.018). Across adulthood, CAF concentrations were negatively associated with grip strength and SMI (both P<0.001). In people ≥50years old, CAF concentrations were 22.6% higher in those with sarcopenia (P<0.001), 11.3% higher in those with low SMI (P=0.006) and 9.6% higher in those with low grip strength (P=0.0034), compared with controls. People in the highest CAF concentration quartile, had 3.25 greater odds for sarcopenia (95% CI=1.41-7.49, P=0.005), 2.76 greater odds for low SMI (95% CI=1.24-5.22, P=0.012), and 2.56 greater odds for low grip strength (95% CI=1.07-5.57, P=0.037), compared with those in the lowest quartile. People with a CAF Z-score ≥2 had 9.52 greater odds for sarcopenia (95% CI=3.01-30.05, P<0.001) compared with a Z-score <1. Plasma CAF concentration had an acceptable level of diagnostic accuracy for sarcopenia (AUC=0.772, 95% CI=0.733-0.807, P<0.001). The reference values presented herein may guide the clinical interpretation of circulating CAF and help identify people at risk of poor skeletal muscle outcomes for inclusion in therapeutic interventions. Our findings add clarity to existing data, demonstrating a robust relationship between circulating CAF and skeletal muscle integrity in the largest adult cohort to date, and support the use of CAF as an accessible, cost-effective screening tool for sarcopenia. However, further research into the prognostic utility of plasma CAF, and the establishment of normative data from other populations, are urgently needed if routine CAF screening is to be embedded into public healthcare settings.

Evolving brain network dynamics in early childhood: Insights from modular graph metrics

Modular dynamic graph theory metrics effectively capture the patterns of dynamic information interaction during human brain development. While existing research has employed modular algorithms to examine the overall impact of dynamic changes in community structure throughout development, there is a notable gap in understanding the cross-community dynamic changes within different functional networks during early childhood and their potential contributions to the efficiency of brain information transmission. This study seeks to address this gap by tracing the trajectories of cross-community structural changes within early childhood functional networks and modeling their contributions to information transmission efficiency. We analyzed 194 functional imaging scans from 83 children aged 2 to 8 years, who participated in passive viewing functional magnetic resonance imaging sessions. Utilizing sliding windows and modular algorithms, we evaluated three spatiotemporal metrics—temporal flexibility, spatiotemporal diversity, and within-community spatiotemporal diversity—and four centrality metrics: within-community degree centrality, eigenvector centrality, between-community degree centrality, and between-community eigenvector centrality. Mixed-effects linear models revealed significant age-related increases in the temporal flexibility of the default mode network (DMN), executive control network (ECN), and salience network (SN), indicating frequent adjustments in community structure within these networks during early childhood. Additionally, the spatiotemporal diversity of the SN also displayed significant age-related increases, highlighting its broad pattern of cross-community dynamic interactions. Conversely, within-community spatiotemporal diversity in the language network exhibited significant age-related decreases, reflecting the network's gradual functional specialization. Furthermore, our findings indicated significant age-related increases in between-community degree centrality across the DMN, ECN, SN, language network, and dorsal attention network, while between-community eigenvector centrality also increased significantly for the DMN, ECN, and SN. However, within-community eigenvector centrality remained stable across all functional networks during early childhood. These results suggest that while centrality of cross-community interactions in early childhood functional networks increases, centrality within communities remains stable. Finally, mediation analysis was conducted to explore the relationships between age, brain dynamic graph metrics, and both global and local efficiency based on community structure. The results indicated that the dynamic graph metrics of the SN primarily mediated the relationship between age and the decrease in global efficiency, while those of the DMN, language network, ECN, dorsal attention network, and SN primarily mediated the relationship between age and the increase in local efficiency. This pattern suggests a developmental trajectory in early childhood from global information integration to local information segregation, with the SN playing a pivotal role in this transformation. This study provides novel insights into the mechanisms by which early childhood brain functional development impacts information transmission efficiency through cross-community adjustments in functional networks.

Age-adjusted CSF t-tau and NfL do not improve diagnostic accuracy for prodromal Alzheimer’s disease

Cerebrospinal fluid total-tau (t-tau) and neurofilament light chain (NfL) are biomarkers of neurodegeneration and are increased in Alzheimer’s disease (AD). In order to adjust for age-related increases in t-tau and NfL, cross-sectional age-adjusted norms were developed based on amyloid negative cognitively normal (CN) adults aged 41–78 years (CN, n = 137). The age-adjusted norms for t-tau and NfL did not improve receiver operating curve based diagnostic accuracies in individuals with mild cognitive impairment (MCI) due to AD (AD-MCI, n = 144). Furthermore, while NfL was correlated with higher age in AD-MCI, no significant correlation was found for t-tau. The cox proportional hazard models, applied in 429 participants with baseline t-tau and NfL, showed higher hazard ratio of progression to MCI or dementia without age-adjustments (HR = 3.39 for t-tau and HR = 3.17 for NfL), as compared to using our norms (HR = 2.29 for t-tau and HR = 1.89 for NfL). Our results indicate that utilizing normative reference data could obscure significant age-related increases in these markers associated with neurodegeneration and AD leading to a potential loss of overall diagnostic accuracy.

Exploring ocular fibulin-3 (EFEMP1): Anatomical, age-related, and species perspectives

Fibulin-3 (FBLN3, aka EFEMP1) is a secreted extracellular matrix (ECM) glycoprotein implicated in ocular diseases including glaucoma and age-related macular degeneration. Yet surprisingly, little is known about its native biology, expression patterns, and localization in the eye. To overcome these shortcomings, we conducted gene expression analysis and immunohistochemistry for FBLN3 in ocular tissues from mice, pigs, non-human primates, and humans. Moreover, we evaluated age-related changes in FBLN3 and FBLN3-related ECM remodeling enzymes/inhibitors in aging mice. We found that FBLN3 displayed distinct staining patterns consistent across the mouse retina, particularly in the ganglion cell layer and inner nuclear layer (INL). In contrast, human retinas exhibited a unique staining pattern, with enrichment of FBLN3 in the retinal pigment epithelium (RPE), INL, and outer nuclear layer (ONL) in the peripheral retina. This staining transitioned to the outer plexiform layer (OPL) in the central retina/macula, and was accompanied by reduced RPE immunoreactivity approaching the fovea. Surprisingly, we found significant age-related increases in FBLN3 expression and protein abundance in the mouse retina which was paralleled by reduced transcript levels of FBLN3-degrading enzymes (i.e., Mmp2 and Htra1). Our findings highlight important species-dependent, retinal region-specific, and age-related expression and localization patterns of FBLN3 which favor its accumulation during aging. These findings contribute to a better understanding of FBLN3's role in ocular pathology and provide valuable insights for future FBLN3 research.

Age-related enhancement of the association between episodic memory and gray matter volume in medial temporal and frontal lobes

BackgroundEpisodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer’s disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative.ResultThe present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males.ConclusionsOur study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals.

Artificial intelligence enhanced ophthalmological screening in children: insights from a cohort study in Lubelskie Voivodeship

This study aims to investigate the prevalence of visual impairments, such as myopia, hyperopia, and astigmatism, among school-age children (7–9 years) in Lubelskie Voivodeship (Republic of Poland) and apply artificial intelligence (AI) in the detection of severe ocular diseases. A total of 1049 participants (1.7% of the total child population in the region) were examined through a combination of standardized visual acuity tests, autorefraction, and assessment of fundus images by a convolutional neural network (CNN) model. The results from this artificial intelligence (AI) model were juxtaposed with assessments conducted by two experienced ophthalmologists to gauge the model's accuracy. The results demonstrated myopia, hyperopia, and astigmatism prevalences of 3.7%, 16.9%, and 7.8%, respectively, with myopia showing a significant age-related increase and hyperopia decreasing with age. The AI model performance was evaluated using the Dice coefficient, reaching 93.3%, indicating that the CNN model was highly accurate. The study underscores the utility of AI in the early detection and diagnosis of severe ocular diseases, providing a foundation for future research to improve paediatric ophthalmic screening and treatment outcomes.

Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age.

Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers), degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum, as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and 24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences. The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated (Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed age-related changes in both sexes, with greater prominence in females. Aged females had significantly higher serum cholesterol (p < 0.05), jejunum cholesterol (p < 0.05), and serum plant sterols (p < 0.05). They exhibited poorer hepato-intestinal health compared with males, which was characterized by mild liver dysfunction (hydropic degeneration, increased serum ALT, p < 0.05, and decreased activity of some antioxidant defense enzymes, p < 0.05), mononuclear inflammation in the jejunal lamina propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity (p < 0.05). Aged females showed increased levels of 27-hydroxycholesterol (p < 0.05) and upregulated ERα gene expression (p < 0.05) in the liver. Our study suggests that the more significant age-related increase in serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver.

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function.

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood. The prefrontal cortex (PFC) is known to mediate EF and WM and is an area that shows a vulnerability to age-related alterations in neuronal morphology. In the current study, we show that performance on EF and WM tasks exhibited significant changes with age, and these impairments correlate with changes in biophysical properties of layer 3 (L3) pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of L3 LPFC pyramidal neurons, consistent with previous studies. Further, this age-related hyperexcitability of LPFC neurons was significantly correlated with age-related decline on a task of WM, but not an EF task. The current study characterizes age-related performance on tasks of WM and EF and provides insight into the neural substrates that may underlie changes in both WM and EF with age.

Age-related differences in resting-state functional connectivity from childhood to adolescence.

The human brain is active at rest, and spontaneous fluctuations in functional MRI BOLD signals reveal an intrinsic functional architecture. During childhood and adolescence, functional networks undergo varying patterns of maturation, and measures of functional connectivity within and between networks differ as a function of age. However, many aspects of these developmental patterns (e.g. trajectory shape and directionality) remain unresolved. In the present study, we characterised age-related differences in within- and between-network resting-state functional connectivity (rsFC) and integration (i.e. participation coefficient, PC) in a large cross-sectional sample of children and adolescents (n=628) aged 8-21years from the Lifespan Human Connectome Project in Development. We found evidence for both linear and non-linear differences in cortical, subcortical, and cerebellar rsFC, as well as integration, that varied by age. Additionally, we found that sex moderated the relationship between age and putamen integration where males displayed significant age-related increases in putamen PC compared with females. Taken together, these results provide evidence for complex, non-linear differences in some brain systems during development.

Aging of the Nose: A Quantitative Analysis of Nasal Soft Tissue and Bone on Computed Tomography.

Morphologic and anatomical changes of the aging nose affect the surgical strategy of rhinoplasty in older patients, but age-related changes in noses have yet to be fully characterized. This study aimed to determine the evolution of nasal soft tissue and bone in aging noses using computed tomography. Computed tomographic images of 200 Asian patients were included. The study population was divided into two groups according to age and sex: a younger group (20 to 35 years of age) and an older group (65 to 80 years of age). Measurements of nasal soft tissue and bone on computed tomography were performed using Osirix 9.0 software. With regard to soft-tissue changes, the nasal skin and soft-tissue envelope thickness at rhinion, supratip, and nasal tip increased significantly with aging in both sexes. Increase of nasal depth and decrease of nasolabial angle were significant in both sexes. Nasal length and nasofrontal angle showed significant age-related increases in men; decrease of nasal tip angle and increase of pyramidal angle were significant in women. With regard to nasal bone changes, the bone length decreased significantly in women and the bone thickness decreased significantly in both sexes. Nasofrontal angle in men and pyramidal angle in women increased significantly. These results suggest that the aging process leads to drooping of the nasal tip, thickened nasal skin and soft tissue, and resorption of the nasal bone, providing a reference for rhinoplasty in older patients.

Age-Related Changes in Facial Soft Tissue of Han Chinese: A Computed Tomographic Study.

Facial lifting and volume restoration are the major strategies of facial rejuvenation, but the aging of facial soft tissues has not been sufficiently explored. This study aimed to reveal the age-related changes in full facial soft tissue of Han Chinese by using computed tomography. The measurements were performed on head computed tomographic images of 200 Han Chinese subjects (100 men and 100 women). The thickness of facial soft tissue was measured at 20 anthropological landmarks of the skull. The thickness at rhinion was increased, whereas the thickness at midphiltrum, supradentale, and infradentale was decreased, indicating the significant differences in both sexes. Besides, the thickness at glabella, nasion, supramentale, and menton was decreased significantly in women. The thickness at supraorbital and lateral orbit was increased with aging in either sex. The thickness at frontal eminence, infraorbital, supraglenoid, and gonion showed significant age-related increases in women, and the thickness at zygomatic arch, supra M2, and infra M2 was significantly decreased in men. These results suggest that soft tissues in different areas of the face are selectively thickened or thinned with aging, thus providing a reference for rejuvenation procedures.

Speech representation used by Mandarin Chinese-speaking children aged three to six years.

This study investigates how Mandarin Chinese-speaking children use Mandarin Chinese, a language lacking tense markers, to represent characters' speech in their story narratives. Eighty participants, from three to six years of age, completed an elicited narrative task based on a wordless picture book. The representing forms and signals that they employed in representing activities were assessed. The results showed a significant age-related increase in the overall use of speech representation by the cohort of children. Regarding representing forms, direct representation exhibited its expected dominance among all age groups, and its presence in children's narratives grew significantly with age. Concerning representing signals, shuō 'say' was the most prevalent across all ages and susceptible to significant age effects, and, with advancing age, children's representing signals expanded from single verbs to more complex syntactic constructions. In addition, no significant gender effects were observed regarding the representing forms or signals that Mandarin-speaking children used.

Spin Lattice (T1) and Magnetization Transfer Saturation (MTsat) Imaging to Monitor Age-Related Differences in Skeletal Muscle Tissue.

Background: The aim was to compare spin-lattice relaxation (T1) mapping from sequences with no fat suppression and three fat suppression methods and Magnetization Transfer Saturation (MTsat) mapping, to identify regional and age-related differences in calf muscle. These differences may be of clinical significance in age-related loss of muscle force. Methods: Ten young and seven senior subjects were imaged on a 3T MRI scanner using a 3D Fast Low Angle Shot sequence without and with different fat suppression and with MT saturation pulse. Bland–Altman plots were used to assess T1 maps using the fat unsuppressed sequence as the reference image. Age and regional differences in T1 and in MTsat were assessed using two-way factorial analyses of variance (ANOVAs) with Bonferroni-adjusted independent sample t-tests for post hoc analyses. Results: A significant age-related increase in T1 and decrease in MTsat was seen in the calf muscles. The largest size effect was observed in the T1 sequence with fat saturation. Conclusions: T1 increase with age may reflect increase in inflammatory processes while the decrease in MTsat may indicate that magnetization transfer may also be associated with muscle fiber macromolecules. T1 and MTsat maps of calf muscle have the potential to detect regional and age-related compositional differences in calf muscle.

Establishment of Age-Specific Whole Blood Biochemistry and Gas Reference Intervals in Broiler Chickens using the i-STAT and the Vetscan VS2 Portable Analyzers.

Whole blood biochemistry and blood gas analysis are uncommonly used in poultry, but their use could improve the diagnosis of certain diseases or aid in monitoring flock health. To create preliminary reference intervals for selected blood analytes in broilers using the i-STAT and Vetscan VS2 (VS2) portable analyzers, we tested broilers at 7, 21, and 35 days of age. A total of 134 venous blood samples from healthy chickens of two different flocks were analyzed. There were significant age-related increases in concentration for glucose, hematocrit, ionized calcium, sodium, and carbon dioxide partial pressure on the i-STAT and for aspartate aminotransferase, creatine kinase, total calcium, phosphorus, and total protein on the VS2. Conversely, significant decreases in concentration were observed for pH, oxygen partial pressure, oxygen saturation on the i-STAT and for uric acid and albumin on the VS2. Additionally, significant differences were found on some blood parameters among the two flocks. Extremely high CK values were found on broilers after 21 days of age, indicating a possible degree of muscle injury during the grow-out. Preliminary reference intervals for all the analytes at each of the age groups were obtained. This study's data provide a starting point for the interpretation of blood analysis in broiler chickens at different ages and offer a new approach to investigate certain metabolic diseases that affect commercial poultry.

Biochemical reference intervals in broiler chickens according to age and strain

Abstract. The objective of the research was to study the physiological pattern of biochemical variables and to obtain reference intervals for young (less than 1 month) and adult (more than 1 month) broiler chickens of 2 strains. From the jugular vein, blood for analysis was collected, separated, and then immediately analyzed. The influence of age was significant for the majority of the investigated variables in the 2 groups. In Isa15 strain, a significant age-related decrease in plasma uric acid, glucose, cholesterol, triglycerides, phosphorus, potassium and iron was established. Also, a significant age-related increase in plasma calcium and ASAT was obtained in the same broiler strain. In Arbor Acres Plus strain, a significant age-related decrease in plasma glucose, cholesterol, triglycerides and phosphorus was observed. A significant age-related increase in plasma total protein, calcium and ASAT has also been reported in this broiler strain. A significant difference between the two strains was reported for plasma uric acid, glucose, cholesterol, phosphorus, magnesium and iron (p&lt;0.05). For most estimated parameters in the 2 strains, calculation of separate reference intervals for young and adult animals was appropriate. Except for potassium in young Isa15 strain, and phosphorus in young Arbor Acres Plus strain, all variables did not follow a normal distribution. Reference intervals are presented for both ages using non-parametric or robust method. 90% confidence intervals for both groups were calculated non-parametrically, or by the bootstraping method. The established reference intervals will be a useful guide for interpreting plasma biochemical variables in different strains of broiler chickens raised in Algeria, and reared in a mild Mediterranean climate.

Increased ERb expression during ageing could be neuroprotective against Alzheimer's disease development in the male but not the female brain.

Age is the biggest risk factor for Alzheimer's disease (AD) with cases doubling every 5 years after 65 years. Increased risk is also associated with being female. This gender difference in AD incidence could be partly explained by menopause-related hormone deficiencies during ageing. Clinical studies concluded that the age when hormone replacement therapy was started, especially after the menopause, was critical in delaying AD development. Deposition of b-amyloid (Ab) in the hippocampus and cortex is the key pathological feature in AD. Much evidence has demonstrated that oestrogen activation of oestrogen receptors (ER) in neurones decreases Ab accumulation and antagonizes its cytotoxic effects in AD. ERb is an ER subtype highly expressed in the nervous system. In vivo studies reported that ERb activation reduces the cytotoxic effect of Ab through the Akt pathway and improves learning and memory capacity in AD models. However, this finding has not yet been investigated in the clinic. We hypothesised that the increased risk of AD in women could be partly explained by alterations in the levels of oestrogen, its receptors and downstream signalling pathways in the female brain during ageing affecting the expression of AD biomarkers. Levels of ERb, phosphorylated and total Akt, APP, its secretases and metabolites were measured using immunoblotting and ELISA in frontal cortical brain samples from young (20-30), middle-aged (45-55) and old (70-90) men and women with no history of dementia. In female brains significant age-related increases in APP and the secretases were observed but were not seen in male samples. bCTF and the Aβ42:40 ratio also showed age-related increases only in women. Aβ42 levels were higher in elderly female samples compared to male. In contrast, significant age-related increases in ERb and pAkt:total Akt were only seen in male samples. We demonstrate for the first time a sex difference in the expression of AD biomarkers with ageing with a novel age-related increase in APP in the ageing female brain. The increase in ERb expression in male but not female samples could result in a neuroprotective effect against Aβ cytotoxicity. Our findings could partly explain female vulnerability for AD development.

Traumatic Brain Injury Induces cGAS Activation and Type I Interferon Signaling in Aged Mice.

Aging adversely affects inflammatory processes in the brain, which has important implications in the progression of neurodegenerative disease. Following traumatic brain injury (TBI), aged animals exhibit worsened neurological function and exacerbated microglial-associated neuroinflammation. Type I Interferons (IFN-I) contribute to the development of TBI neuropathology. Further, the Cyclic GMP-AMP Synthase (cGAS) and Stimulator of Interferon Genes (STING) pathway, a key inducer of IFN-I responses, has been implicated in neuroinflammatory activity in several age-related neurodegenerative diseases. Here, we set out to investigate the effects of TBI on cGAS/STING activation, IFN-I signaling and neuroinflammation in young and aged C57Bl/6 male mice. Using a controlled cortical impact model, we evaluated transcriptomic changes in the injured cortex at 24 hours post-injury, and confirmed activation of key neuroinflammatory pathways in biochemical studies. TBI induced changes were highly enriched for transcripts that were involved in inflammatory responses to stress and host defense. Deeper analysis revealed that TBI increased expression of IFN-I related genes (e.g. Ifnb1, Irf7, Ifi204, Isg15) and IFN-I signaling in the injured cortex of aged compared to young mice. There was also a significant age-related increase in the activation of the DNA-recognition pathway, cGAS, which is a key mechanism to propagate IFN-I responses. Finally, enhanced IFN-I signaling in the aged TBI brain was confirmed by increased phosphorylation of STAT1, an important IFN-I effector molecule. This age-related activation of cGAS and IFN-I signaling may prove to be a mechanistic link between microglial-associated neuroinflammation and neurodegeneration in the aged TBI brain.