Age-related Variations Research Articles

The Influence of Age, Sex, and Season on Hematological Parameters in a Captive Population of Former Laboratory Chimpanzees (Pan troglodytes).

This study aimed to establish a baseline hematological profile and examine the influence of age, sex, and season on hematological parameters in captive chimpanzees (Pan troglodytes) living in a humid tropical climate. Hematological parameters are a useful tool for assessing health status and diagnosing diseases in animals. We analyzed 473 blood samples collected from 84 chimpanzees (43 females and 41 males) during annual health checks, conducted under anesthesia for a routine physical examination. The main findings revealed significant sex differences in some hematological parameters: males had higher hematocrit and red blood cell counts than females. Age-related variations have also been noted, with adolescents and adults having lower lymphocyte counts but higher neutrophil and monocyte counts than infants. Adults, in particular, had significantly lower platelet counts compared to other age classes. Seasonal fluctuations were also observed: lymphocyte counts were higher in the rainy season, while neutrophil counts were higher in the dry season. In addition, the general trends in hematological parameters for this captive population of chimpanzees were similar to those reported in captive chimpanzees living in the United States. These results should provide animal health professionals, particularly those working with nonhuman primates, with data to compare and interpret. They will help improve practices for monitoring and managing the health of nonhuman primates in captivity.

Differences in clinical, radiological and laboratory parameters between elderly and young patients with newly diagnosed smear-positive pulmonary tuberculosis in Vietnam.

To investigate the differences in clinical, radiological and laboratory parameters between elderly and young patients with newly diagnosed smear-positive pulmonary tuberculosis in Vietnam. This retrospective analysis included all patients hospitalised with newly diagnosed pulmonary tuberculosis with acid-fast bacilli-positive smear. Clinical symptoms, laboratory results and chest X-ray findings were collected using a standardised questionnaire. Elderly was defined as those patients aged 65 years and older. A total of 183 patients diagnosed with new acid-fast bacilli-positive pulmonary tuberculosis were included in this study, with a mean age of 56.2 ± 16.3 years (minimum = 18 and maximum = 87 years). Seventy-seven participants were aged ≥65 years, accounting for 42.1% of participants. A total of 147 (80.3%) patients were male, and the sex ratio of male/female was 4.1. Night sweats were statistically more frequent among younger patients (34.9% vs. 20.8%, p = 0.04), whereas muscle and joint pain were more predominant among the elderly (7.6% vs. 22.1%, p = 0.01). A proportion of 67.0% of younger patients and 63.6% of the elderly group were bilaterally affected. Cavitation lesions were significantly more frequent in the younger group (55.7% vs. 39.0%, p = 0.03), whereas pulmonary fibrosis occurred more frequently in elderly patients (29.3% vs. 45.4%, p = 0.02). No other significant differences in clinical symptoms, laboratory results and chest X-ray findings were observed. These findings underscore the importance of considering age-related variations in the clinical and radiological presentation of tuberculosis, which can guide tailored approaches in diagnosis, management and treatment strategies for different age groups.

Decoding Age-Related Changes in Emotional Reactivity: The Importance of Distinguishing Positive and Negative Sensations

This study investigated age-related variations in emotional reactivity, focusing on the differentiation between positive and negative emotional sensations. Grounded in Socioemotional Selectivity Theory (SST), we hypothesized that older vs. younger adults would exhibit heightened valence and intensity in their emotional sensations, alongside increased co-occurrence of positive and negative sensations. We presented 100 negative, 100 neutral, and 100 positive images to 67 young adults and 72 older adults. Utilizing unipolar scales enabled a nuanced analysis of emotional reactivity. Our findings revealed that older vs. younger adults overall report: 1) more positive and negative sensations, with a predominance for positive sensations, particularly when faced with positive images; 2) more intense sensations, regardless of the valence of the images; 3) more complex emotional sensations, particularly when faced with negative images. Thus, our findings validated the key principles of SST and can be seen as a manifestation of an adaptive strategy developed in older adults to promote richer, more positive emotional experiences. However, the study’s broader implications are moderated by certain limitations. The experimental sample shows a gender imbalance, with a predominance of females and a lack of racial, ethnic and socio-economic diversity in older adults. In addition, the low- to medium-intensity emotional stimuli reflect only a narrow spectrum of everyday experiences. These constraints underscore the need for future research to encompass greater demographic inclusion and a wider range of emotional stimuli to ensure the applicability of our findings to more complex populations and emotional landscapes.

Cephalomedullary Nails for Isolated Subtrochanteric Femur Fractures: Age-Related Variations in Fracture Pattern and Perioperative Factors Do Not Affect Clinical and Radiographic Outcomes

Cephalomedullary Nails for Isolated Subtrochanteric Femur Fractures: Age-Related Variations in Fracture Pattern and Perioperative Factors Do Not Affect Clinical and Radiographic Outcomes

Sex and Age Differences in the Impact of Metabolic Syndrome on Heart Failure Development

Metabolic syndrome (MetS), a cluster of metabolic dysregulations, is recognized as a significant risk factor for the development of heart failure (HF). The pathophysiological mechanisms linking MetS to HF are complex and multifaceted, with the components of MetS contributing to cardiac deterioration through impaired myocardial energy metabolism, increased inflammation, and endothelial dysfunction. Numerous clinical studies have confirmed the relationship between MetS and HF. Multiple studies have demonstrated that the impact of MetS on HF varies by sex and age. Metabolic disorders, including MetS, have a greater impact on HF incidence in younger adults compared to the elderly population and in women compared to men. Although the reasons for these differences are not yet fully understood, recognizing the sex- and age-related variations is crucial for developing targeted strategies to prevent HF in individuals with MetS. Future research should continue to investigate the underlying mechanisms behind these variations and identify optimal management approaches that account for both sex and age in reducing HF risk.

Age-related differences in psychopathology within sex chromosome trisomies.

Sex chromosome trisomies (SCTs) are a group of genetic disorders characterized by presence of a supernumerary sex chromosome, resulting in karyotypes other than XX or XY. These include XXX (Trisomy X), XXY (Klinefelter syndrome), and XYY (Jacobs syndrome). Sex chromosome trisomies have been linked to increased risk for psychopathology; however, this relationship warrants additional research. Specifically, little is known regarding potential age-related variation in risk for psychopathology and how this may differ across karyotypes and subdomains of psychopathology, which has relevance for psychoeducation, personalized care, and mechanistic research. Thus, we used the Child Behavior Checklist (CBCL) to estimate age-related variation in psychopathology in a large cross-sectional sample of individuals with SCTs (n = 201) and euploidic controls (n = 304) spanning the age range of 5-18 years. We found that elevations of psychopathology in SCT were significantly associated with age in a manner that varied as a combined function of the karyotype and CBCL scale being considered. Post hoc tests revealed there is a uniquely pronounced age-associated increase in severity of social problems in XYY, alongside a lack of statistical evidence for age-related variation in the severity of psychopathology for other CBCL domains and SCT karyotypes. Our findings are relevant for advancing the personalization of clinical assessment and monitoring in SCTs. They also highlight potential windows of dynamic risk emergence for closer clinical and biological study, as well as opportunities to provide intervention to mitigate future risk.

Reduced Vestibular Function is Associated with Cortical Surface Shape Changes in the Frontal Cortex.

Aging-associated decline in peripheral vestibular function is linked to deficits in executive ability, self-motion perception, and motor planning and execution. While these behaviors are known to rely on the sensorimotor and frontal cortices, the precise pathways involving the frontal and sensorimotor cortices in these vestibular-associated behaviors are unknown. To fill this knowledge gap, this cross-sectional study investigates the relationship between age-related variation in vestibular function and surface shape alterations of the frontal and sensorimotor cortices, considering age, intracranial volume, and sex. Data from 117 participants aged 60+ from the Baltimore Longitudinal Study of Aging, who underwent endorgan-specific vestibular tests (cVEMP for the saccule, oVEMP for the utricle, and vHIT for the horizontal canal) and T1-weighted MRI scans on the same visit, were analyzed. We examined ten brain structures in the putative "vestibular cortex": the middle-superior part of the prefrontal cortex (SFG_PFC), frontal pole (SFG_pole), and posterior pars of the superior frontal gyrus (SFG), the dorsal prefrontal cortex and posterior pars of middle frontal gyrus (MFG_DPFC, MFG), the pars opercularis, pars triangularis, and pars orbitalis of the inferior frontal gyrus, as well as the precentral gyrus and postcentral gyrus (PoCG) of the sensorimotor cortex. For each region of interest (ROI), shape descriptors were estimated as local compressions and expansions of the population average ROI surface using surface LDDMM. Shape descriptors were linearly regressed onto standardized vestibular variables, age, intracranial volume, and sex. Lower utricular function was linked with surface compression in the left MFG and expansion in the bilateral SFG_pole and left SFG. Reduced canal function was associated with surface compression in the right SFG_PFC and SFG_pole and left SFG. Both reduced saccular and utricular function correlated with surface compression in the posterior medial part of the left MFG. Our findings illuminate the complexity of the relationship between vestibular function and the morphology of the frontal and sensorimotor cortices in aging. Improved understanding of these relationships could help in developing interventions to enhance quality of life in aging and populations with cognitive impairment.

Dietary contributions in the genetic variation of liver fibrosis: a genome-wide association study of fibrosis-4 index in the liver fibrosis development

BackgroundThe fibrosis-4 (FIB-4) index is a non-invasive method to assess the severity of liver fibrosis. The development of liver fibrosis is influenced by genetic predisposition and dietary factors. However, the modulating effect of dietary factors on the genetic susceptibility of liver fibrosis remains unclear. The study aims to investigate the role of dietary factors in modulating the genetic susceptibility of liver fibrosis.MethodsHere, we conducted a genome-wide association study (GWAS) of FIB-4 index-directed liver fibrosis risk, adjusted with diet, lifestyle factors, and hepatitis serological markers. The high (N = 1,476) and low (N = 36,735) liver fibrosis risk groups were defined with a FIB-4 > 2.67 and < 1.3, respectively.ResultsThe age-related FIB-4 variation showed subjects with a FIB-4 > 2.67 (3.8%), indicating high fibrosis risk, occurred predominantly among individuals above 60 years old. The multivariable analysis showed that tea intake is significantly associated with a reduced risk of liver fibrosis. The GWAS adjusted for sex, age, age2, dietary factors (tea and coffee consumption, vegetarian preference), lifestyle (alcohol consumption, physical activity), hepatitis serological markers (anti-HCV, HBsAg, HBeAg), and the top ten principal components indicated 25 genome-wide significant signals (p < 5 × 10− 8). Two variants (rs56293029 and rs9389269) were previously associated with the FIB-4 index in alcohol-related cirrhosis, while the 23 SNPs remaining were novel. The rs9399136 (HBS1L) is a protective variant, and rs9274407 (HLA-DQB1) is a risk variant, both contributing to liver fibrosis development. Our results showed that genetic factors play a major role in liver fibrosis, while dietary factors have minor effects on disease progression. Pathway analysis suggested the potential of immune response and hematopoietic systems function in the pathogenesis of liver disease.ConclusionsThe studies not only revealed the protective role of rs9399136 (HBS1L) and the risk effect of rs9274407 (HLA-DQB1) toward liver fibrosis in a Taiwanese population, but also demonstrated that individual consumption patterns, such as tea uptake, have a minor impact on liver fibrosis prevention. The pathway analysis from GWAS variants further indicated the importance of immune responses in the pathogenesis of liver fibrosis.

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 &lt; 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.

A novel statistical framework for meta-analysis of total mediation effect with high-dimensional omics mediators in large-scale genomic consortia.

Meta-analysis is used to aggregate the effects of interest across multiple studies, while its methodology is largely underexplored in mediation analysis, particularly in estimating the total mediation effect of high-dimensional omics mediators. Large-scale genomic consortia, such as the Trans-Omics for Precision Medicine (TOPMed) program, comprise multiple cohorts with diverse technologies to elucidate the genetic architecture and biological mechanisms underlying complex human traits and diseases. Leveraging the recent established asymptotic standard error of the R-squared (R2)-based mediation effect estimation for high-dimensional omics mediators, we have developed a novel meta-analysis framework requiring only summary statistics and allowing inter-study heterogeneity. Whereas the proposed meta-analysis can uniquely evaluate and account for potential effect heterogeneity across studies due to, for example, varying genomic profiling platforms, our extensive simulations showed that the developed method was more computationally efficient and yielded satisfactory operating characteristics comparable to analysis of the pooled individual-level data when there was no inter-study heterogeneity. We applied the developed method to 5 TOPMed studies with over 5800 participants to estimate the mediation effects of gene expression on age-related variation in systolic blood pressure and sex-related variation in high-density lipoprotein (HDL) cholesterol. The proposed method is available in R package MetaR2M on GitHub.

Body fat variation and redistribution across different stages of life measured by dual-energy x-ray absorptiometry.

The global obesity epidemic of all ages has increased the demand for accurate management of body fat in each stage of life. The primary aim of this study was to provide reference centiles of body fat indices for Chinese children and adults and compare those with ethnicities from USA using dual-energy x-ray absorptiometry (DXA). The samples were drawn from two nationwide cross-sectional surveys of China Body Composition Life-course Study (2013-2023) and the US National Health and Nutrition Examination Survey (2011-2018). Age- and sex-specific centile curves were generated for a set of fat measurements, including total fat mass (FM), fat mass index (FMI), body fat percentage (BF%), trunk-to-leg fat ratio (TLR), android-to-gynoid fat ratio (AGR) and visceral-to-subcutaneous fat ratio (VSR), using the general additive model for location scale and shape method. The age-related variations from childhood to adulthood were generally similar among Chinese, Non-Hispanic Whites, Non-Hispanic Blacks and Mexican American population, with distinct levels across races and ethnicities. For whole-body fat (FM, FMI, and BF%), Mexican American population consistently presented the highest levels before 40 years old, followed by Non-Hispanic White, Non-Hispanic Black and Chinese individuals. For central fats indices, although the TLR and AGR levels in Chinese males were second to Mexican American counterparts in most stages of life, the VSR was much higher in Chinese than other races and ethnicities from eight years old. DXA-based centiles for body fat quantity and distribution in Chinese population aged 3-60 years old were presented, and their differences with other race and ethnicity were noted across periods from early childhood to middle adulthood. Our findings will promote age-, sex- and ethnic-specific assessment of life-course body fat and obesity-related risks in clinical practice.

Finds of skulls of juvenile &lt;I&gt;Kurdalagonus maicopicus&lt;/I&gt; (Сetacea, Cetotheriidae) in the upper Miocene of the Republic of Adygea

Fragments of two skulls of young cetotherium baleen whales have been described from the Fortep’yanka 2 locality (Russia, Republic of Adygea, Maikop district, Fortep’yanka river valley, Upper Miocene, Upper Sarmatian, Blinovskaya Formation). Based on the morphology of the posterior (mastoid) process of the petrous bone, the structure of the posterior edge of the temporal fenestra, and the S-shaped shape of the superoccipital ridges, the finds were attributed to Kurdalagonus maicopicus (Spasskii, 1951). The proportions of the skull and the degree of closure of the sutures of the skull made it possible to determine the individual age of these whales within a year. New findings significantly complement the data on the structure of the sutures of the lateral wall of the skull and age-related variability of cranial morphology in representatives of the genus Kurdalagonus.

Relationship between the microstructural energy release rate of cortical bone and age under compression condition

Most studies evaluated the energy release rate of cortical bone macrostructure under Mode I, Mode II, and mixed Mode I-II loading conditions. However, testing the macrostructural energy release rate requires an initial crack and recording the applied load and the corresponding crack length in real-time, which may introduce measurement errors and differences with the actual fracture scenarios. To further understand how the energy release rate contributed to the cortical bone fracture characteristics, this study predicted the microstructural energy release rate of cortical bone and then investigated its age-related varitions. The microstructural energy release rate of femoral cortical bone in rats from different ages was back-calculated by fitting the experimental and simulated load–displacement curves under compression load. The trends in the microstructural energy release rate were revealed, and the underlying reasons for the age-related changes were investigated by integrating the discussion on the cortical bone mechanical parameters at various levels obtained from the previous experiment. The predicted microstructural energy release rate of femoral cortical bone in the rats from 1, 3, 5, 7, 9, 11, and 15 months of age were in the range of 0.08–0.12, 0.12–0.14, 0.15–0.19, 0.25–0.28, 0.23–0.25, 0.19–0.22, and 0.13–0.16 N/mm, respectively. The statistical analyses showed the significant differences in the microstructural energy release rate at different ages. The results indicated an increasing trend followed by a decrease from 1 to 15 months of age, and the correlations between microstructural energy release rate and age were significant. The age-related variations in the microstructural energy release rate may be linked to the changes in the microarchitecture, and the fracture load is influenced by the micro-level mechanical parameters. Notably, the age-related trends in microarchitecture and energy release rate were similar. These findings were valuable for understanding the mechanism underlying the weakening mechanical properties of cortical bone microstructure with age from an energy perspective.

The Spleen Modulates the Balance of Natural and Pathological Autoantibodies in a Mouse Model of Autoimmune Arthritis.

Natural autoantibodies (natAAbs) react with evolutionarily conserved antigens but they do not lead to pathological tissue destruction, contrary to pathological autoantibodies (pathAAbs). NatAAbs usually belong to the IgM isotype, and their network, also known as the "immunological homunculus", is thought to play a role in immunological tolerance. NatAAbs are produced by B1 cells found mostly on the serosa surfaces or the spleen. The exact relation between natAAbs and pathAAbs is still not completely understood. The recombinant human proteoglycan (PG) aggrecan G1 domain (rhG1)-induced arthritis (GIA) is an excellent mouse model for rheumatoid arthritis because it represents most of the clinical, immunological and laboratory parameters of the corresponding human pathology. Recently, we studied the role of the spleen in GIA, and found that a splenectomy modified the development of autoimmunity. To further characterize the possible role of the nAAb levels in tolerance and autoimmunity, in the present study, we set out to measure the nat- and pathAAb levels in GIA. We analyzed the natAAb levels in the serum against cartilage PG aggrecan, Hsp60 and Hsp70, and the mitochondrial citrate synthase (CS) antigens in healthy control and arthritic mice. Furthermore, we studied whether the splenectomy influenced the production of nat- and pathAAbs in mice with GIA. Our results show that the natAAb levels against PG aggrecan, Hsp60, Hsp70 and CS showed age-related variations in healthy BALB/c mice. The induction of autoimmune arthritis did not change the levels of the measured natAAbs significantly. Splenectomy, on the other hand, clearly decreased the levels of all the measured natAAbs. Interestingly, the levels of the pathAAbs showed the opposite change: they were higher in the splenectomized group than in the control arthritic mice. Based on these results, we conclude that the spleen plays a role in setting the balance between nat- and pathAAbs in autoimmune arthritis.

Age, sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model.

We evaluated the impact of sex and mitochondrial-haplotype on the age-related changes in the fecal gut microbiome of the genetically heterogeneous rodent model, the OKC-HETB/W rat. Alpha-diversity, measuring richness and evenness of gut microbiome composition, did not change with age or mitochondrial-haplotype. However, beta-diversity, a measure of microbial differences among samples, was significantly modulated by age in male and female rats in both mitochondrial-haplotypes. The age-related changes in the microbiome differed markedly between male and female rats. Five microbial species changed significantly with age in male rats compared to nine microbial species in female rats. Only three of these microbes changed with age in both male and female rats. The mitochondrial-haplotype of the rats also affected how aging altered the microbiome. Interestingly, most of the microbial species that changed significantly with age were mitochondrial-haplotype and sex specific, i.e., changing in one sex and not the other. We also discovered that sex and mitochondrial-haplotype significantly affected the age-related variations in content of fecal short-chain fatty acids and plasma metabolites that influence or are regulated by the microbiome, e.g., tryptophan derived metabolites and bile acids. This study demonstrates that the host's sex plays a significant role in how the gut microbiome evolves with age, even within a genetically diverse background. Importantly, this is the first study to show that the mitochondrial-haplotype of a host impacts the age-related changes in the microbiome and supports previous studies suggesting a bidirectional interaction between the gut microbiome and host mitochondria.

Gender and age-related variations in rumen fermentation and microbiota of Qinchuan cattle.

Our study aimed to investigate the gender and age-related variations in rumen fermentation, serum metabolites, and microbiota in Qinchuan cattle. A total of 38 Qinchuan beef cattle were selected and maintained on a uniform diet for three months. Rumen fluid and blood samples were collected to determine rumen fermentation, serum metabolites, and microbial 16S rRNA sequencing. The results revealed that the concentration of rumen butyrate in female Qinchuan cattle was significantly higher than in males (P<0.05). Isobutyrate, butyrate, and isovalerate exhibited significant age-related differences. Females exhibited lower serum GLU and higher TG, NEFA levels compared to males (P<0.05). Serum ALB and UREA levels increased with age (P<0.05). Furthermore, the alpha diversity of rumen bacteria improved with age (P<0.05), with no gender differences observed. Males had higher relative abundances of Bacteroidota, Verrucomicrobiota, and Cyanobacteria, while females had higher Firmicutes and Desulfobacterota (P<0.05). The cellulose-degrading genus Ruminococcus and propionate-producing genus Succiniclasticum were more abundant in females, whereas the anti-inflammatory genus Lachnospiraceae_NK4A136_group and the hemicellulose-degrading genus Prevotella were more abundant in males (P<0.05). Age-related differences in bacteria were found in Pseudobutyrivibrio and several members of the Lachnospiraceae. Functional prediction indicated that "Amino acid metabolism" and "Lipid metabolism" were mainly enriched in females, whereas "Carbohydrate metabolism" and "Glycan biosynthesis and metabolism" were enriched in males (P<0.05). RDA analysis highlighted butyrate as a key factor influencing the rumen bacterial community. NK4A214_group and Ruminococcus were positively correlated with butyrate, while Prevotella and Pseudobutyrivibrio were negatively correlated with butyrate (P<0.05). We observed a significant improvement in the diversity and stability of rumen microbiota as age increased. Ruminococcus, NK4A214_group, and Prevotella were likely contributors to variations in energy utilization and fat deposition between male and female Qinchuan cattle.

Differential temporal decline of cerebral oxytocin and μ-opioid receptor density during the aging process in mice.

Aging is often associated with changes in social, sexual, emotional and pain functioning, as well as with the increased prevalence of certain psychopathologies. However, the neurodevelopmental basis underpinning these age-related changes remains to be determined. Considering the key roles of oxytocin (OTR) and μ-opioid (MOPr) receptor systems in regulating social, sexual, pain, reward and emotional processing, it seems plausible that they are also implicated in age-related behavioural alterations. Although the ontogeny of both receptors has been well characterized in rodent brains from early development till adulthood, little is known concerning the neuroadaptations occurring from middle age to old age. Therefore, we mapped the neuroadaptations in OTR and MOPr in the brains of mice at those developmental endpoints. Quantitative OTR and MOPr autoradiographic binding was carried out in the brains of male mice at 2, 6, 9, 12 and 18 months of age. A significant whole brain decline in OTR density was detected between 2 and 6months of age, with no additional decline thereafter. Interestingly, for MOPrs, the decline in density was not detected until 9months of age. Region-specific age-related decline in OTR density was concentrated in the lateral anterior olfactory nuclei (AOL) and, for MOPr, in the AOL and the nucleus accumbens for MOPr. Identifying the tipping point of these age-related variations in both receptors may assist with our understanding of the neurobiology underlining age-related changes in social, pain and emotional functioning/processing. It may also help us target interventions to specific developmental windows to abrogate certain age-related psychopathologies.

A review of artificial intelligence-based brain age estimation and its applications for related diseases.

The study of brain age has emerged over the past decade, aiming to estimate a person's age based on brain imaging scans. Ideally, predicted brain age should match chronological age in healthy individuals. However, brain structure and function change in the presence of brain-related diseases. Consequently, brain age also changes in affected individuals, making the brain age gap (BAG)-the difference between brain age and chronological age-a potential biomarker for brain health, early screening, and identifying age-related cognitive decline and disorders. With the recent successes of artificial intelligence in healthcare, it is essential to track the latest advancements and highlight promising directions. This review paper presents recent machine learning techniques used in brain age estimation (BAE) studies. Typically, BAE models involve developing a machine learning regression model to capture age-related variations in brain structure from imaging scans of healthy individuals and automatically predict brain age for new subjects. The process also involves estimating BAG as a measure of brain health. While we discuss recent clinical applications of BAE methods, we also review studies of biological age that can be integrated into BAE research. Finally, we point out the current limitations of BAE's studies.

Investigation of inter-subject variation in ultrafine particle deposition across human nasal airways: A study involving children, adults, and the elderly

The airflow and particle dynamics in adult nasal airways have been extensively investigated, but the impact of age-related anatomical changes in children and the elderly remains underexplored. This study systematically investigates age-related anatomical variations and associated influence on nasal airflow dynamics and ultrafine particle deposition characteristics by using Computational Fluid-Particle Dynamics (CFPD) approach. Numerical simulations were conducted for 9 healthy nasal subjects spanning a wide age range. 6 Nasal subjects from the Development Group were used as the primary models for data analysis and deposition correlation development, while 3 subjects from the Validation Group were used to validate the reliability of the derived total and subregional deposition correlations. Our results reveal distinctive variations across age groups. Specifically, the elderly and children exhibit unique patterns that differ from those of young adults. While total deposition efficiency differs significantly between children and adults, filtration efficiency in the subregion with most deposition, main respiratory, remains consistent. Lastly, overall and subregional empirical equations for deposition efficiency were developed by incorporating the combined diffusion parameter, Sca∆b, corroborating the use of geometrical characteristic parameters for each specific subject in predicting nasal deposition efficiency across different age groups. Our findings are expected to improve the predictive nanoparticle exposure analysis in nasal airways across different age groups, thereby improving the respiratory health for individuals throughout the life span.

Speeding up interval estimation for R2-based mediation effect of high-dimensional mediators via cross-fitting.

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed iterative Sure Independence Screening (iSIS) in two subsamples to exclude the non-mediators, followed by ordinary least squares regressions for the variance estimation. We then constructed confidence intervals based on the newly derived closed-form asymptotic distribution of the R2 measure. Extensive simulation studies demonstrated that this proposed procedure is much more computationally efficient than the resampling-based method, with comparable coverage probability. Furthermore, when applied to the Framingham Heart Study, the proposed method replicated the established finding of gene expression mediating age-related variation in systolic blood pressure and identified the role of gene expression profiles in the relationship between sex and high-density lipoprotein cholesterol level. The proposed estimation procedure is implemented in R package CFR2M.