Chronological Age Research Articles

Frailty Status, Not Just Age, is Associated With Postoperative Opioid Consumption: A Retrospective, Population-based Analysis

Objective: To assess the relationship between postoperative opioid consumption and frailty status. Background: Physiologic reserve can be assessed through both chronologic age as well as measures of frailty. Although prior studies suggest that older individuals may require less opioid following surgery, chronologic age, and frailty do not always align, and little is known regarding postoperative opioid consumption patterns by frailty. Methods: We conducted a retrospective analysis of opioid-naïve adult patients undergoing common general, vascular, and gynecologic procedures across a statewide quality improvement program from November 6, 2017 to February 28, 2021. Our primary outcome was postoperative patient-reported opioid consumption within 30 days of surgery in oral morphine equivalents (OME). Our primary exposure was frailty status defined by the modified frailty index (mFi-5) criteria. Other covariates included patient demographic and clinical attributes, procedural factors, discharge opioid prescription size, and postoperative complications. Linear regression was performed to assess the association of frailty status and opioid consumption, stratified by age. Results: In this cohort of 34,854 patients, 10,596 had an mFi-5 score of ≤1 and 3,635 had a score of >1. A score of >1 was associated with increased patient-reported opioid consumption (OMEs 3.3 greater; 95% CI = 1.5–5.1). This held true for individuals over 65 (OMEs 2.7 greater; 95% CI = 0.2–5.1). Frailty status, regardless of score, was negatively associated with an opioid prescription at discharge. Conclusions: Frailty status is associated with increased opioid consumption after common operations. Future prescribing guidelines and outcomes analyses should consider this marker when reviewing opioid consumption data and related adverse outcomes.

Reconstructing infant mortality in Iberian Iron Age populations from tooth histology

The Neonatal Line (NNL) of the tooth serves as a unique identifier, allowing us to distinguish whether a child survived birth. This line is essential for assessing the age at death of infants from skeletal remains found in archaeological contexts. Our primary objective is to accurately determine the age of infant intramural inhumations from the Iberian Iron Age (8th-1st centuries BC) by analyzing histological sections of tooth germs. Due to their fragility and high susceptibility to taphonomic factors, these samples are challenging to handle. By accurately assessing their age, we aim to classify individuals into various stages of infant mortality, which will help reconstruct infant mortality patterns in these populations.We analyze unerupted and still-forming crown deciduous teeth from 45 infant burials. By calculating Crown Formation Time (CFT) and identifying the NNL, we determine both gestational and chronological ages. We further validate the reliability of NNL identification through Synchrotron X-ray Fluorescence (SXRF) elemental analysis (Ca, Zn, Cu) on two contemporary and two archaeological samples.Our histological study reveals the chronological age of 38 infants from Iberian settlements, ranging from the 30th week of gestation to the 2nd postnatal month. The age distribution shows an attritional mortality pattern, with nearly half experiencing perinatal mortality, including preterm births. These findings support the hypothesis that mortality was primarily attributed to natural causes. Our research enhances the understanding of infant life history events in prehistory by combining histological analysis of tooth NNL and CFT, highlighting the technique's potential and limitations.

Factors related to spontaneous space closure following early first permanent molar extraction: A systematic review.

Dental caries and molar-incisor hypomineralization (MIH) are primary reasons for the extraction of first permanent molars (M1) in children, which can lead to significant dental and facial development issues such as a midline shift and temporomandibular joint disorder. This systematic review aimed to identify key factors influencing spontaneous space closure following the early extraction of first permanent molars (M1) in children aged 5-15. We conducted a comprehensive search across Scopus, PubMed, Dimensions, Web of Science, and Cochrane databases, including the literature from 1960 to 2024. The inclusion criteria focused on clinical trials, case-control, cross-sectional, cohort studies, and case series that evaluated the impact of various factors on the spontaneous closure after M1 extraction. The analysis highlights that chronological age and the developmental stage of the second permanent molars (M2) at the time of extraction are significant predictors of successful spontaneous space closure. Additionally, the presence and angle of M2, along with the presence of third permanent molars (M3), play crucial roles but require further investigation. Early assessment of M2's developmental stage and inclination, and the presence of M3 are essential for enhancing the likelihood of successful spontaneous space closure following M1 extraction in children.

Topical Platelet Exosomes Reduce Senescence Signaling in Human Skin: An Exploratory Prospective Trial.

Cellular senescence, an irreversible cell cycle arrest with secretory phenotype, is a hallmark of skin aging. Regenerative exosome-based approaches, such as topical human platelet extract (HPE), are emerging to target age-related skin dysfunction. To evaluate the cellular and molecular effects of topical HPE for skin rejuvenation after 12 weeks of twice daily use. Skin biopsies were obtained for histological evaluation of senescence markers, p16INK4a and p21CIP1/WAF1. Telomere-associated foci, coassociation of telomeres, and DNA damage marker, γH2AX, were assessed. RNA sequencing evaluated senescence associated secretory phenotype (SASP) and extracellular matrix pathways. p16INK4a and p21CIP1/WAF1 staining in senescent skin cells revealed low and high expression subgroups that did not correspond to chronological age. Topical HPE significantly reduced high p16INK4a cells in the dermis (p = .02). There was also a decrease in telomere damage after topical HPE (p = .03). In patients with high senescent cells at baseline, there was a 40% reduction in proinflammatory SASP. Extracellular matrix remodeling pathways, including collagen and elastic fibers, were up-regulated. Topical HPE, applied on intact skin, reduced senescence signaling and senescence-associated telomere damage after 12 weeks of twice daily use, targeting a path for skin longevity or healthy skin aging.

Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome.

With aging, the body's ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in immunoglobulin G (IgG) glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of white men from Europe, aged 29-45years, under treatment with metformin, testosterone, metformin plus testosterone, and placebo (trial registration number NCT02514629, 2013/07/04), and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.

Subjective and functional outcome measures to evaluate performance of pediatric cochlear implant

BackgroundThe majority of research on the effects of cochlear implants has been on clinical evaluations of efficacy (hearing and speech skills and auditory thresholds). But it is unclear how much clinical efficacy metrics (speech, hearing, and language tests) actually demonstrate how beneficial cochlear implants (CI) are in everyday circumstances. In this study, we aim to assess the performance of a child’s current CI with both subjective and functional outcomes measures. Also, we aimed to assess factors affecting these outcomes after CI.MethodsThe study group included 45 cochlear-implanted children, and their chronological age ranges between 4 and 12 years. Children were divided according to their language age into three groups: group 1 (G1) includes15 children with a language age of less than 2 years, group 2 (G2) includes 15 children with a language age of 2 to less than 4 years, and group 3 (G3) includes 15 children with language age 4 to 6 years. Assessment was done in two sessions: one for phoniatric evaluation and another for audiological evaluation.ResultsCI enabled children to develop speech perception in a closed manner evidenced by the early speech perception (ESP) test with pattern perception being the easiest and monosyllabic words being the most difficult and the least to develop. Most children with CI were able to control their voice, to a lesser extent to use speech in meaningful use in social situations and to develop communication strategies in oral situations which were the least to develop, and this was evident by Meaningful Use of Speech Scale. Children with CI were able to acquire language, and their receptive language was better than expressive language, but their language age was below their chronological age.ConclusionThe cochlear implant is an effective rehabilitative tool for the treatment of prelingually deafened children, and this was evident by our results. A hierarchal approach of speech assessment according to the language age of the child and selection of age-appropriate speech perception test is very important to assess cochlear-implanted children Speech recognition had a high degree of variability. Early implantation age and increased duration of implant experience were the most important factors associated with good performance with CI, better speech perception, and better language outcomes.

Efficacy and Safety of Autologous Stem Cell Transplantation in First-Line Treatment and at Relapse in Elderly Patients with Multiple Myeloma

Introduction: Although recent data suggest that melphalan high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT) is safe and effective in eligible multiple myeloma (MM) patients up to the age of 75 years, its value in elderly MM patients is still controversially discussed. Methods: We retrospectively analyzed 607 MM patients ≥60 years old, who were admitted to our institution for first-line or salvage HDT/ASCT between January 2007 and October 2018. We assigned them to three groups according to age at HDT/ASCT: 60–64 years (S1), 65–69 years (S2) and ≥70 years (S3). We compared progression-free and overall survival, duration of hospitalization, complications, transfers to intermediate or intensive care unit, readmissions after discharge and deaths within 100 days after HDT/ASCT between these groups. Results: Age did not impact progression-free and overall survival after first-line and salvage HDT/ASCT. Patients ≥70 years old at first HDT/ASCT had a longer hospitalization compared to patients 60–64 years old; however, the difference in the length of hospitalization was only marginal. Rates of febrile neutropenia, mucositis, transfers to intermediate or intensive care unit, readmissions after discharge, and deaths within 100 days after HDT/ASCT were similar in the 3 age groups of patients receiving first or salvage HDT/ASCT. Patients with a Charlson Comorbidity Index ≥2 receiving first HDT/ASCT had a higher risk for a transfer to intermediate or intensive care unit. Conclusion: Our analysis shows that HDT/ASCT is safe and effective in eligible elderly MM patients in first-line treatment and at relapse. A careful patient selection according to biological rather than chronological age is of crucial importance.

Accelerated biological aging, mediating amino acids, and risk of incident type 2 diabetes: a prospective cohort study.

Aging plays an important role in type 2 diabetes mellitus (T2DM). But the association between accelerated biological age and T2DM, and the mechanisms underlying this association remains unclear. Thus, this study aimed to examine the associations of biological aging with T2DM, and explore the potential mediation effect of amino acids. This prospective cohort study included 95,773 participants in the UK Biobank who were free of diabetes at baseline. Biological age was measured from clinical traits using PhenoAgeAccel. Cox proportional hazard models were used to estimate the hazard ritios (HRs) and 95% confidence intervals (CIs), and mediation analysis was used to explore the mediation effect of amino acids. During a median follow-up of 14.02 years, 6,347 incident T2DM cases were recorded. After multivariable adjustment for sociodemographic characteristics, lifestyle factors, and other risk factors of T2DM, participants with older biological age were at increased risk of incident T2DM (30% increase per standard deviation of PhenoAgeAccel, 95% CI: 28.0-33.0%). Additionally, higher branched chain amino acids (BCAAs) including isoleucine and leucine, aromatic amino acids (AAAs) including phenylalanine and tyrosine, were associated with increased PhenoAgeAccel and risk of incident T2DM; while glutamine and glycine were inversely associated. Alanine, glutamine, glycine, phenylalanine, tyrosine, isoleucine, leucine, and total concentration of branched-chain amnio acids could partially explain the associations between PhenoAgeAccel and T2DM. Accelerated biological aging was associated with increased risk of incident T2DM independent of chronological age and may be a risk factor of T2DM, partially mediated by several amino acids.

Examining Health Behaviors as Mechanisms Linking Earlier Pubertal Timing with Accelerated Epigenetic Aging in Late Adolescence.

Earlier pubertal timing is associated with accelerated epigenetic aging, but the underlying mechanisms are not well understood. This three-wave longitudinal study examined negative health behaviors, specifically substance use, short sleep duration, and poor diet quality in middle adolescence, as mediators of links between earlier phenotypic and perceived pubertal timing measured in early adolescence and epigenetic aging on three epigenetic clocks in late adolescence (GrimAge, DunedinPACE, and PhenoAge). Phenotypic pubertal timing measured physical pubertal maturation relative to chronological age, whereas perceived pubertal timing was based on adolescents' subjective interpretation of their pubertal timing relative to their peers. Participants included 1213 youth (51% female, 49% male; 62% Black, 34% White) who participated during early adolescence (mean age = 13.10 years), middle adolescence (mean age = 16.1 years) and late adolescence (mean age = 19.7 years). Results from a mediation model revealed a mediation effect of earlier phenotypic pubertal timing on accelerated GrimAge in late adolescence through higher substance use during middle adolescence. There was also a direct effect of earlier phenotypic pubertal timing on accelerated DunedinPACE in males. Sleep duration and diet quality did not emerge as mediators but shorter sleep duration predicted accelerated GrimAge in females. These findings suggest that higher substance use presents a mechanism through which earlier maturing youth experience faster epigenetic aging that puts them at risk for poorer health across the lifespan.

Life-Course Socioeconomic Trajectories and Biological Aging: The Importance of Lifestyles and Physical Wellbeing

Background/Objectives: Studies investigating the associations between life-course socioeconomic status (SES) and biological aging (the difference between biological and chronological age, Δage) have mostly been focused on epigenetic clocks and on a limited number of mediators. The aim of this study was to investigate this relationship using a blood-based aging clock, as well as the potential mediation of different factors including lifestyles or their proxies and physical and mental wellbeing. Methods: A deep-learning aging clock based on 36 blood markers was deployed, in a large Italian population cohort: the Moli-sani study (N = 4772; ≥35 years; 48% men). SES was defined as an eight-level trajectory over the life course, which was tested with Δage in linear models incrementally adjusted for age, sex, and prevalent health conditions. Moreover, the proportion of associations explained by diverse potential mediators, including diet, smoking, physical activity, alcohol, body mass index (BMI), and physical and mental quality of life (QoL) was estimated. Results: Compared to participants with a stably high SES, those showing an educational and financial downward trajectory were older than their CA (β (95%CI) = 1.28 (0.73–1.83) years), as were those with a stably low SES (0.75 (0.25–01.25) years). These associations were largely explained by the tested mediators (overall proportion: 36.2% and 66.3%, respectively), prominently by physical QoL (20.7% and 41.0%), BMI (16.8% and 34.3%), lifestyle (10.6% and 24.6%), and dietary inflammatory score (5.3% and 9.2%). Conclusions: These findings indicate that life-course socioeconomic inequalities are associated with accelerated biological aging, suggesting physical wellbeing and pro-inflammatory lifestyles as potential public health targets to slow down this process in susceptible socioeconomic strata of the population.

Age-dependent prevalence of malocclusions requiring treatment according to the KIG classification : Amultipart cross-sectional study over a10-year period from the district of Viersen/North Rhine.

Patients with statutory health insurance (SHI) in Germany must undergo an assessment of orthodontic treatment need using the "Kieferorthopädische Indikationsgruppen" (KIG; orthodontic indication groups) classification system since 2002. Atreatment need only exists if anomalies of acertain degree of severity are present. The aim of this study was to evaluate the age-dependent prevalence and percentage distribution of KIG grades requiring treatment in patients with SHI before the age of 18over a10-year period. Between 2012 and 2021, treatment indication existed for 1951 (1025female, 926male) out of 2288 patients with SHI in the cohort of this study before the age of 18according to current SHI guidelines. The KIG classification was based on the highest existing KIG grade. There were no multiple classifications. The patient cohort was divided into three patient groups (PG) according to chronological age for analysis: PG1 < 10years of age (early treatment), PG2 10 to < 13years of age (main treatment) and PG3 13 to < 18years of age (late treatment). In PG1 (454 patients), the KIG classificationsD(26.5%), K(25.5%), M(19.4%), and P(18.0%) dominated. In PG2 (998 patients), classifications D(33.2%), predominated, whereas K(7.5%) and M(5.9%) rarely occurred. The classifications E(12.6%) and P(13.3%) appeared quite frequently. Transverse deviations occurred only about half as often in PG2 as in PG1 and PG3. In PG3 (499patients), the classification E(17.6%) was particularly common, while P(2.6%) was rare. The proportion of KIG grades 5decreased depending on age: 19% in PG1, 13.5% in PG2, 10.4% in PG3. The prevalence of sagittal classifications was highest in all age groups (45.9% in PG1, 39.1% in PG2, 31.5% in PG3). The distribution of KIG classifications requiring treatment was not homogeneous, but age dependent. The differences were particularly evident in the early treatment group and may be due to the limited applicability of the KIG classification system in patients before late mixed dentition. With increasing age at initial examination, the prevalence of sagittal classifications decreased, while that of vertical classifications increased. Still, the sagittal classifications DandM occurred most frequently in all age groups. The KIG classification Dwas always the most common in all patients until the age of18.

Clinical characteristics and management status of Turner syndrome in 1 089 children

Objective: To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China. Methods: As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed. Results: Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years. Conclusions: The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

18F]FDG PET integrated with structural MRI for accurate brain age prediction.

Brain aging is a complex and heterogeneous process characterized by both structural and functional decline. This study aimed to establish a novel deep learning (DL) method for predicting brain age by utilizing structural and metabolic imaging data. The dataset comprised participants from both the Universal Medical Imaging Diagnostic Center (UMIDC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The former recruited 395 normal control (NC) subjects, while the latter included 438 NC subjects, 51 mild cognitive impairment (MCI) subjects, and 56 Alzheimer's disease (AD) subjects. We developed a novel dual-pathway, 3D simple fully convolutional network (Dual-SFCNeXt) to estimate brain age using [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and structural magnetic resonance imaging (sMRI) images of NC subjects as input. Several prevailing DL models were trained and tested using either MRI or PET data for comparison. Model accuracies were evaluated using mean absolute error (MAE) and Pearson's correlation coefficient (r). Brain age gap (BAG), deviations of brain age from chronologic age, was correlated with cognitive assessments in MCI and AD subjects. Both PET- and MRI-based models achieved high prediction accuracy. The leading model was the SFCNeXt (the single-pathway version) for PET (MAE = 2.92, r = 0.96) and MRI (MAE = 3.23, r = 0.95) on all samples. By integrating both PET and MRI images, the Dual-SFCNeXt demonstrated significantly improved accuracy (MAE = 2.37, r = 0.97) compared to all single-modality models. Significantly higher BAG was observed in both the AD (P < 0.0001) and MCI (P < 0.0001) groups compared to the NC group. BAG correlated significantly with Mini-Mental State Examination (MMSE) scores (r=-0.390 for AD, r=-0.436 for MCI) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores (r = 0.333 for AD, r = 0.372 for MCI). The integration of [18F]FDG PET with structural MRI enhances the accuracy of brain age prediction, potentially introducing a new avenue for related multimodal brain age prediction studies.

A biological age based on common clinical markers predicts health trajectory and mortality risk in dogs.

Predicting aging trajectories through biomarkers of biological aging can guide interventions that optimize healthy lifespan in humans and companion animals. Differences in physiology, genetics, nutrition, and lifestyle limit the generalization of such biomarkers and may therefore require species-specific algorithms. Here, we compared correlations of standard clinical blood parameters with survival probability in humans with those of the two most common mammalian companion animals, cats and dogs, and highlighted universal and species-specific relationships. Based on this comparative analysis, we generated and validated an algorithm that predicts biological age in canines using a longitudinal dataset with health records, blood count, and clinical chemistry from 829 dogs spanning over 12years. Positive deviations of biological from chronological age (AgeDev) measured by this composite score significantly correlated with a decreased survival probability (hazard ratio = 1.75 per 1year of AgeDev, p = 3.7e - 06). Importantly, in nearly half of the dogs whose biological age was accelerated by more than 1year, none or only a single individual marker scored outside its respective reference range, suggesting practical applications for the detection of unfavorable health trajectories. Analyzing samples from a unique 14-year life-long diet restriction study, we show that restricted caloric intake lowers biological age, an effect that can be quantified at midlife years before a difference in survival is observed. Thus, a biological age clock based on clinical blood tests predicts the health trajectories of dogs for use in research and veterinary practice.

Magnetic Resonance Images for the Prediction of Chronological Age Using Maxillary Third Molar Teeth: An Observational Study.

Dental age estimation using third molars is a reliable method for estimating the age of individuals. Recently, magnetic resonance imaging (MRI) of the head and neck has been found to be applicable for age estimation of third molar teeth. In the present study, we aimed to apply the Modified Demirjian method of age estimation to magnetic resonance (MR) image sections for dental age estimation by determining the mineralization patterns of the maxillary third molars. MRI scans of the patients were performed using SIGNA™ 3.0Tesla MRI GE Healthcare (Chicago, USA) with a moving, multifunctional coil. Two expert radiologists with more than three years of experience independently analyzed the image sections using the open-source Digital Imaging and Communications in Medicine (DICOM) viewer software. The age and sex of the patients whose images were included in the study were recorded using a specially designed proforma. The stage of development of the maxillary third molars was determined using the modified Demirjian method. Inter observer agreement was calculated using the intra class correlation coefficient. Simple linear regression analysis was used to predict the actual age at the third molar development stage. There was excellent agreement between observers (ICC =0.99 (95% CI = 0.98-0.99)). There was also a significant association between the maxillary third molar tooth development stage and chronological age of the individual (P=0.001; B=1.54; 95% CI = 0.71-2.37). The findings from the present study establish that the Modified Demirjian method can also be reliably applied for dental age assessment in MR sections.

Changes in health-related quality of life in young-old and old-old patients undergoing elective orthopedic surgery: A systematic review.

There is a significant gap in research exploring changes in postoperative health-related quality of life (HRQoL) among patients aged 65 years and older undergoing hip or knee arthroplasty. To investigate the variations in HRQoL improvement, as evaluated by patient-reported outcome measures following total hip arthroplasty, total knee arthroplasty, and partial knee arthroplasty between the young-old and old-old adults. We searched six online databases (including MEDLINE, Embase) from their inception dates to May 15, 2023. We included studies using a validated HRQoL assessment tool to evaluate changes in HRQoL in patients aged ≥65 years undergoing hip or knee arthroplasty. These include the EuroQol five-dimension (EQ-5D), Short Form 36 (SF-36) and Short Form 12 (SF-12). The primary outcomes were postoperative HRQoL changes between young-old (65-74 years) and old-old groups (≥75 years). The secondary outcomes included complications, length of stay, and mortality. The search yielded 12,229 articles; twelve studies (n = 103,613) were included. Studies using EQ-5D found no significant differences between young-old and old-old patients after hip and knee arthroplasty. Analyses of SF-36 and SF-12 scales showed no significant age-related differences in postoperative improvements in physical and mental health. Our review of four studies that included multivariable analyses revealed inconsistent associations between age and EQ-5D. Comparisons between the young-old and old-old age groups in postoperative complications, hospital length of stay, and mortality revealed no associated age-related changes in HRQoL. The young-old and old-old patients exhibited comparable improvement in HRQoL following hip or knee arthroplasty. The older patients did not have higher postoperative complications rates, longer hospital length of stay, and increased mortality. While chronological age should be considered when planning hip and knee arthroplasty, greater emphasis should be placed on assessing the comorbidities and functional status of patients.

Network-level enrichment provides a framework for biological interpretation of machine learning results.

Machine learning algorithms are increasingly being utilized to identify brain connectivity biomarkers linked to behavioral and clinical outcomes. However, research often prioritizes prediction accuracy at the expense of biological interpretability, and inconsistent implementation of ML methods may hinder model accuracy. To address this, our paper introduces a network-level enrichment approach, which integrates brain system organization in the context of connectome-wide statistical analysis to reveal network-level links between brain connectivity and behavior. To demonstrate the efficacy of this approach, we used linear support vector regression (LSVR) models to examine the relationship between resting-state functional connectivity networks and chronological age. We compared network-level associations based on raw LSVR weights to those produced from the forward and inverse models. Results indicated that not accounting for shared family variance inflated prediction performance, the k-best feature selection via Pearson correlation reduced accuracy and reliability, and raw LSVR model weights produced network-level associations that deviated from the significant brain systems identified by forward and inverse models. Our findings offer crucial insights for applying machine learning to neuroimaging data, emphasizing the value of network enrichment for biological interpretation.

Retro-age: A unique epigenetic biomarker of aging captured by DNA methylation states of retroelements.

Reactivation of retroelements in the human genome has been linked to aging. However, whether the epigenetic state of specific retroelements can predict chronological age remains unknown. We provide evidence that locus-specific retroelement DNA methylation can be used to create retroelement-based epigenetic clocks that accurately measure chronological age in the immune system, across human tissues, and pan-mammalian species. We also developed a highly accurate retroelement epigenetic clock compatible with EPICv.2.0 data that was constructed from CpGs that did not overlap with existing first- and second-generation epigenetic clocks, suggesting a unique signal for epigenetic clocks not previously captured. We found retroelement-based epigenetic clocks were reversed during transient epigenetic reprogramming, accelerated in people living with HIV-1, and responsive to antiretroviral therapy. Our findings highlight the utility of retroelement-based biomarkers of aging and support a renewed emphasis on the role of retroelements in geroscience.

Epigenetic Clock at Birth and Childhood Blood Pressure Trajectory: A Prospective Birth Cohort Study.

The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown. This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions. Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (β=-2.02; P=0.02) but not in girls (β=-0.49; P=0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; βEAA=-2.95; βIAA=-3.00; P<0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73-0.81; P<0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26-1.38; P<0.01). Significant sex differences were observed (Psex-interaction<2×10-16). GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.

Development of white matter in young adulthood: The speed of brain aging and its relationship with changes in fractional anisotropy

White matter (WM) development has been studied extensively, but most studies used cross-sectional data, and to the best of our knowledge, none of them considered the possible effects of biological (vs. chronological) age. Therefore, we conducted a longitudinal multimodal study of WM development and studied changes in fractional anisotropy (FA) in the different WM tracts and their relationship with cortical thickness-based measures of brain aging in young adulthood. A total of 105 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort underwent magnetic resonance imaging (MRI) at the age of 23-24, and the age of 28-30 years. At both time points, FA in the different WM tracts was extracted using the JHU atlas, and brain age gap estimate (BrainAGE) was calculated using the Neuroanatomical Age Prediction using R (NAPR) model based on cortical thickness maps. Changes in FA and the speed of cortical brain aging were calculated as the difference between the respective variables in the late vs. early 20s. We demonstrated tract-specific increases as well as decreases in FA, which indicate that the WM microstructure continues to develop in the third decade of life. Moreover, the significant interaction between the speed of cortical brain aging, tract, and sex on mean FA revealed that a greater speed of cortical brain aging in young adulthood predicted greater decreases in FA in the bilateral cingulum and left superior longitudinal fasciculus in young adult men. Overall, these changes in FA in the WM tracts in young adulthood point out the protracted development of WM microstructure, particularly in men.