Chronological Age Research Articles

Synergistic Impact of 25-Hydroxyvitamin D Concentrations and Physical Activity on Delaying Aging

ObjectiveOur study aims to examine the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and physical activity (PA) status with phenotypic age (PhenoAge). MethodThe analysis included 18,738 participants from the NHANES 2007-2010 & 2015-2018. Phenotypic Age Acceleration (PhenoAgeAccel) was calculated as the residuals from regressing PhenoAge on chronological age. Weighted multivariable logistic regression models were used to analysis the relationship between 25(OH)D and PA with PhenoAgeAccel. Population attributable fraction (PAF) was used to estimate the proportion of PhenoAgeAccel which could be avoided if exposure were eliminated. ResultsThe multivariate-adjusted OR (95%CI) for PhenoAgeAccel with high 25(OH)D and adequate PA were 0.657 (0.549,0.787) (p<0.001) for all, 0.663 (0.538,0.818) (p<0.001) for participants whose age ≤ 65years old. Furthermore, there was multiplicative interaction between 25(OH)D and PA in age ≤ 65 years old group (0.729 (0.542,0.979), p = 0.036). High 25(OH)D level and adequate PA reduced the risk of PhenoAgeAccel by 14.3% and 14.2%, respectively. Notably, 30.7% decrease was attributable to both high 25(OH)D level and engaging in adequate PA concurrently. Combining 25(OH)D above 80.4 nmol/l with PA decreased PhenoAge by 1.291 years (p<0.001). ConclusionHigher 25(OH)D level was associated with lower risk of biological ageing. Combining 25(OH)D and PA demonstrated enhanced protective effects, especially in middle or young adults. These findings underscore the importance of outdoor PA in slowing down the aging process.

Brain age has limited utility as a biomarker for capturing fluid cognition in older individuals.

One well-known biomarker candidate that supposedly helps capture fluid cognition is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI. To formally evaluate the utility of Brain Age for capturing fluid cognition, we built 26 age-prediction models for Brain Age based on different combinations of MRI modalities, using the Human Connectome Project in Aging (n=504, 36-100 years old). First, based on commonality analyses, we found a large overlap between Brain Age and chronological age: Brain Age could uniquely add only around 1.6% in explaining variation in fluid cognition over and above chronological age. Second, the age-prediction models that performed better at predicting chronological age did NOT necessarily create better Brain Age for capturing fluid cognition over and above chronological age. Instead, better-performing age-prediction models created Brain Age that overlapped larger with chronological age, up to around 29% out of 32%, in explaining fluid cognition. Third, Brain Age missed around 11% of the total variation in fluid cognition that could have been explained by the brain variation. That is, directly predicting fluid cognition from brain MRI data (instead of relying on Brain Age and chronological age) could lead to around a 1/3-time improvement of the total variation explained. Accordingly, we demonstrated the limited utility of Brain Age as a biomarker for fluid cognition and made some suggestions to ensure the utility of Brain Age in explaining fluid cognition and other phenotypes of interest.

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.

Feeling older, feeling pain? Reciprocal between-person and within-person associations of pain and subjective age in the second half of life.

Experiencing pain in middle adulthood and old age might be interpreted as a sign of aging and make people feel older, whereas feeling older has behavioral, motivational, and physiological consequences that might increase the risk of pain. We investigated between-person and within-person associations between pain, subjective age, and chronological age in middle-aged and older adults. Data from the German Ageing Survey were used (n = 13,874 who provided more than 32,000 observations, baseline mean age = 62.3 years). The observation period comprised up to 13 years (M = 4 years) and five (M = 2.4) measurement occasions. Based on the longitudinal multilevel regression models, we found significant between-person and within-person effects in both directions, which were small but robust when controlling for sociodemographic variables, depressive symptoms, and number of chronic diseases. At the between-person level, participants reporting overall more severe pain also felt older than others. Likewise, those who felt overall older than others reported more pain. At the within-person level, when participants experienced more pain than they usually do, they also reported feeling older than usual. Likewise, on measurement occasions when participants reported feeling older than usual, they reported more pain than usual. Additionally, those with overall stronger pain exhibited steeper age-related increases in their subjective age than those with less severe pain. Our findings suggest that an older subjective age may operate as both antecedent and consequence of pain, and pain might prompt a steeper increase in subjective age over time. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Retinal blood flow association with age and weight in infants at risk for retinopathy of prematurity

This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA) and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP). 38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27 and 47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/− 4.0 IU. BFV positively correlated with PMA (r = 0.3, p = 0.01), CA (r = 0.3, p = 0.005), and CW (r = 0.3, p = 0.02). BFV did not correlate with GA nor BW (r = − 0.2 and r = − 0.05, p > 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (p = 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.

Brain age gap estimation using attention-based ResNet method for Alzheimer’s disease detection

This study investigates the correlation between brain age and chronological age in healthy individuals using brain MRI images, aiming to identify potential biomarkers for neurodegenerative diseases like Alzheimer's. To achieve this, a novel attention-based ResNet method, 3D-Attention-Resent-SVR, is proposed to accurately estimate brain age and distinguish between Cognitively Normal (CN) and Alzheimer’s disease (AD) individuals by computing the brain age gap (BAG). Unlike conventional methods, which often rely on single datasets, our approach addresses potential biases by employing four datasets for training and testing. The results, based on a combined dataset from four public sources comprising 3844 data points, demonstrate the model's efficacy with a mean absolute error (MAE) of 2.05 for brain age gap estimation. Moreover, the model's generalizability is showcased by training on three datasets and testing on a separate one, yielding a remarkable MAE of 2.4. Furthermore, leveraging BAG as the sole biomarker, our method achieves an accuracy of 92% and an AUC of 0.87 in Alzheimer's disease detection on the ADNI dataset. These findings underscore the potential of our approach in assisting with early detection and disease monitoring, emphasizing the strong correlation between BAG and AD.

Anti-CD19 chimeric antigen receptor T-cell therapy in older patients with relapsed or refractory large B-cell lymphoma: A multicenter study.

Chimeric antigen receptor T-cell (CAR-T) therapy, despite being a potentially curative therapy in relapsed or refractory (RR) large B-cell lymphoma (LBCL), remains underutilized in older patients due to limited clinical data. We therefore studied the safety and efficacy of CAR-T therapy in older patients with RR LBCL in the real-world setting. Patients aged ≥65 years with RR LBCL, treated with anti-CD19 CAR-T therapy at 7 US institutions were included in this multicenter, retrospective, observational study. In total, 226 patients were included. Median age at infusion was 71 years (range 65-89). Best objective and complete response rates were 86% and 62%, respectively. Median follow-up after infusion was 18.3 months. The median progression-free survival (PFS) was 6.9 months, with 6- and 12-month PFS estimates of 54% and 44%, respectively. The nonrelapse mortality (NRM) rate was 10.9% at day 180, primarily due to infections, and not impacted by the age groups. Grade ≥3 cytokine release syndrome and neurotoxicity occurred in 7% and 26%, respectively. In univariate analysis, no significant difference in PFS was seen regardless of the age groups or CAR-T type, whereas ECOG PS ≥2, elevated LDH, bulky disease, advanced stage, extranodal involvement, the need for bridging therapy, and prior bendamustine exposure were associated with shorter PFS. These findings support the use of CAR-T in older patients, including those aged ≥80 years. The age at CAR-T therapy did not influence safety, survival, and NRM outcomes. Older patients should not be excluded from receiving CAR-T therapy solely based on their chronological age.

Estimation of chronological age of Risso’s dolphin (Grampus griseus) based on DNA methylation frequency

Age of cetaceans is an important data set for their conservation and management. Although the chronological age of a toothed whale has traditionally estimated from the number of annual tooth growth layer groups (GLGs), this method has potential difficulties such as errors due to the subjectivity of the age-readers and time-consuming sample processing, in addition to lethal tooth sampling in many cases. To overcome these difficulties through a non-lethal approach, considerable amount of efforts has been made in recent years to construct chronological age estimation models based on the correlation between chronological and biological age expressed as the frequency of DNA methylation at CpG (cytosine-phosphate-guanine) sites. The present study, by using next-generation sequencing on DNA extracted from the skin tissues of 30 individuals (15 males and 15 females), performed methylation analysis on multiple CpG sites in the three genes previously reported as age-linked in cetaceans (GRIA2, TET2, and CDKN2A) to construct an age estimation model for Risso’s dolphins. Key aspects of this study are: (1) the chronological ages of Risso’s dolphins of wild origins used in this study had been determined by the GLGs of teeth prior to this study, and (2) as Risso’s dolphins are said to have a lifespan of 30 years, samples were collected from individuals aged 1–29 years, covering from young to old ages. Among the 11 CpG sites in GRIA2, 6 CpG sites in TET2, and 7 CpG sites in CDKN2A analyzed, the CpG sites in GRIA2 showed a statistically significant correlation with age, whereas those in TET2 and CDKN2A did not show such a strong correlation. Using multiple regression analysis on the CpG sites in the three genes, the best fitted model was expressed as follows: y=-0.7548 + 5.6164x(GRIA2_CpG3)+2.6187x(TET2_CpG6)-1.5907x(CDKN2A_CpG3) (R²=0.7062, residual mean=2.98, standard deviation=2.3). With the mean error of 2.98 years between the estimated and known chronological ages, the accuracy of this model was found to be comparable to or higher than that of previously reported age estimation models for cetaceans. This study demonstrated for the future that the age of wild Risso’s dolphins can be estimated by using their skin samples collected with minimal invasiveness.

The impact of age-related hearing loss on cognitive decline: The mediating role of brain age gap

In recent years, the relationship between age-related hearing loss, cognitive decline, and the risk of dementia has garnered significant attention. The significant variability in brain health and aging among individuals of the same chronological age suggests that a measure assessing how one’s brain ages may better explain hearing-cognition links. The main aim of this study was to investigate the mediating role of Brain Age Gap (BAG) in the association between hearing impairment and cognitive function.This research included 185 participants aged 20–79 years. BAG was estimated based on the difference between participant’s brain age (estimated based on their structural T1-weighted MRI scans) and chronological age. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test while hearing ability was measured using pure-tone thresholds (PTT) and words-in-noise (WIN) perception. Mediation analyses were used to examine the mediating role of BAG in the relationship between age-related hearing loss as well as difficulties in WIN perception and cognition.Participants with poorer hearing sensitivity and WIN perception showed lower MoCA scores, but this was an indirect effect. Participants with poorer performance on PTT and WIN tests had larger BAG (accelerated brain aging), and this was associated with poorer performance on the MoCA test. Mediation analyses showed that BAG partially mediated the relationship between age-related hearing loss and cognitive decline.This study enhances our understanding of the interplay among hearing loss, cognition, and BAG, emphasizing the potential value of incorporating brain age assessments in clinical evaluations to gain insights beyond chronological age, thus advancing strategies for preserving cognitive health in aging populations.

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging.

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

Chimeric antigen receptor T-cell therapy in B-cell malignancies and DNA-methylation–based biological aging.

2562 Background: Chimeric antigen receptor T-cell (CAR T-cell) therapy, a type of cancer immunotherapy which leverages genetically altered T cells to target cancer cells, has shown to be an effective option for patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Despite its growing use, the effect of CAR T-cell therapy on the aging process remains limited and findings may have implications for disease relapse and age-related diseases among survivors. The purpose of this study was to investigate the association between CAR T-cell therapy and markers of biological aging. Methods: DNA methylation and clinical data from a publicly available dataset (GSE179414) were used in this analysis. Transduced and untransduced T cells from patients with ALL (n=77) and NHL (n=37) underwent DNA methylation profiling using the Illumina Infinium MethylationEPIC BeadChip. Six DNA methylation-based biological age metrics were calculated: intrinsic epigenetic age acceleration (IEAA), extrinsic epigenetic age acceleration (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), telomere length attrition (TLA), and DunedinPACE (Pace of Aging Calculated from the Epigenome). Multiple linear regression analyses were performed to examine the association between CAR T-cell therapy and the aging metrics by B-cell malignancy. Interaction and stratified analyses by chronological age was additionally performed. Results: DunedinPACE ( P=0.002) was positively associated with CAR T-cell therapy among patients with ALL with an approximately 1-month higher pace of aging in transduced T cells compared to untransduced T cells after adjusting for chronological age and sex. Moreover, chronological age significantly ( P=0.016) modified the association between CAR T-cell therapy and TLA among ALL patients. Specifically, transduced T cells exhibited a 0.46 higher ( P=0.053) and a 0.39 lower ( P=0.142) rate of TLA among patients 16 years of age or older and those younger than 16 years of age, respectively. Conclusions: We observed CAR T-cell therapy was associated with greater biological aging as estimated from DNA methylation among ALL patients and these associations are modified by chronological age. These findings suggest CAR T-cell therapy may be associated with age-related changes to the epigenome in ALL patients and strategies to limit or reverse this effect may have implications for the aging process in cancer survivors. [Table: see text]

Factors Associated with Subjective Aging Among Older Outpatients In Northern - India.

The objective of the study was to investigate factors associated with subjective aging among older patients visiting a geriatric medicine outpatient department in Northern-India. The study is a cross-sectional study. Patients were categorized into three groups: whether they felt younger, equal, or older than their peers of same age. Factors such as fall, incontinence, anorexia, hand grip strength, cognition, depression, vision, hearing, cardiopulmonary function and immunization were assessed. Multinominal logistic regression was used to investigate the associated factors of subjective aging. We assessed 184 older patients with a median age of 66.5 years (IQR 63.0 -78.8). Chronological age and hand grip strength were the significant factors associated with subjective aging. With one year increase in age, odds of feeling older than peers of same age decreased by 8.9% (OR, 0.911; 95% CI, 0.831-0.999, p = 0.047). With one kilogram increase in hand grip strength, odds of feeling younger than peers of same age increased by 7.3% (OR, 1.073; 95% CI, 1.01-1.14, p = 0.032). Chronological age and hand grip strength are the factors associated with subjective aging in Northern-Indian older adults. Further longitudinal multi-center studies are needed to confirm our findings.

Accelerated epigenetic aging and risk of chemotoxicity in older adults with early breast cancer.

1624 Background: Older adults with breast cancer have considerable heterogeneity in their risk of chemotoxicity; two people with the same chronological age have different risks of chemotoxicity. This heterogeneity in chemotoxicity may be due to older adults having variable rates of biological aging. Some older adults age faster biologically compared with their chronological age (i.e., accelerated epigenetic aging [AEA]), while others do not. AEA is a blood biomarker of aging, but its utility as a biomarker of chemotoxicity is unknown. Here, we evaluated the association between AEA and risk of chemotoxicity in older adults with early breast cancer. Methods: In a prospective multicenter study of 397 women age &gt;65 with stage I-III breast cancer treated with neo/adjuvant chemo, we extracted genomic DNA from blood to estimate the participant’s rate of biological aging at baseline (prior to chemotherapy). Using two established epigenetic clocks (AgeAccelGrim and DunedinPACE), we classified individuals as either having AEA or not (dichotomized as a yes/no variable) for each clock. Our primary endpoint was grade 3+ chemotoxicity (yes/no, yes defined as any grade 3+ toxicity attributed to chemo). Using multivariable logistic regression, we examined the association between AEA and grade 3+ chemotoxicity, adjusting for sociodemographic, geriatric, and clinical covariates. Results: The median (range) pretreatment chronological age was 70 (65-85), AgeAccelGrim was -0.88 (-10.4-15.7), and DunedinPACE was 1.03 (0.69-1.45). Of the 397 women, 31 (8%) had AEA per AgeAccelGrim, 63 (16%) had AEA per DunedinPACE, and 184 (46%) experienced grade 3+ chemotoxicity. Women who had evidence of AEA as measured by AgeAccelGrim (≥6.83 years, adjusted OR = 2.73, 95% CI 1.17-6.41, p = 0.02) or DunedinPACE (≥1.17 biological years per chronological year, adjusted OR = 2.20, 95% CI 1.18-4.10, p = 0.01) had greater odds of having grade 3+ chemotoxicity compared to women without AEA (AgeAccelGrim &lt;6.83 or DunedinPACE &lt;1.17, respectively). Conclusions: In this cohort of older women with early breast cancer, those with pre-chemo AEA had increased odds of chemotoxicity compared to women without any evidence of AEA. Future research is needed to examine whether measures of biological age can be translated to the clinical care of older patients with breast cancer. Clinical trial information: NCT01472094 . [Table: see text]

An age-related nomogram for antral follicle counts as a reference guide for reproductive decision making: an observational study of 7573 women

Research questionTo investigate the relationship between antral follicle count (AFC) and chronological age and establish expected values for AFC. DesignThis is a retrospective cohort study at a specialist gynaecological ultrasound centre in London. Women presenting to a gynaecology diagnostic unit for investigation of symptoms or routine check-up, and undergoing transvaginal ultrasound examinations, between the 1st of January 2017 and 22nd of September 2022. ResultsWe analysed 8821 data entries from 7573 women. We estimated the relationship between AFC and age to develop an AFC nomogram independent of the stage in the menstrual cycle. The AFC corresponding to the 10th, 25th, 50th, 75th and 90th centiles for each patient and age group have been calculated. Both nomogram and condition specific populations displayed a gaussian relationship between AFC and age. For the nomogram population, a peak median AFC of 30, was observed between the age groups of 21 -23. The AFC distribution of the previous cystectomy group was found to be statistically different in comparison to the nomogram population(P<0.0001). However, the same did not hold true for those on hormonal contraception (P=0.43). ConclusionsWe provide an AFC nomogram reporting median and interquartile values for AFC by chronological age across the reproductive years. This is a useful tool for providing counselling for those undergoing ovarian reserve assessments taken any time in the menstrual cycle including for those on hormonal contraceptives or previous cystectomy.

Dietary diversity score and the acceleration of biological aging: a population-based study of 88,039 participants

ObjectivesOur study aimed to investigate the association of dietary diversity score (DDS), as reflected by five dietary categories, with biological age acceleration. DesignA cross-sectional study. Setting and participantsThis study included 88,039 individuals from the UK Biobank. MethodsBiological age (BA) was assessed using Klemerae-Doubal (KDM) and PhenoAge methods. The difference between BA and chronological age represents the age acceleration (AgeAccel), termed as “KDMAccel” and “PhenoAgeAccel”. AgeAccel > 0 indicates faster aging. Generalized linear regression models were performed to assess the associations of DDS with AgeAccel. Similar analyses were performed for the five dietary categories. ResultsAfter adjusting for multiple variables, DDS was inversely associated with KDMAccel (βHigh vs Low = −0.403, 95%CI: −0.492 to −0.314, P < 0.001) and PhenoAgeAccel (βHigh vs Low = −0.545, 95%CI: −0.641 to −0.450, P < 0.001). Each 1-point increment in the DDS was associated with a 4.4% lower risk of KDMAccel and a 5.6% lower risk of PhenoAgeAccel. The restricted cubic spline plots demonstrated a non-linear dose-response association between DDS and the risk of AgeAccel. The consumption of grains (βKDMAccel = −0.252, βPhenoAgeAccel = −0.197), vegetables (βKDMAccel = −0.044, βPhenoAgeAccel = −0.077) and fruits (βKDMAccel = −0.179, βPhenoAgeAccel = −0.219) was inversely associated with the two AgeAccel, while meat and protein alternatives (βKDMAccel = 0.091, βPhenoAgeAccel = 0.054) had a positive association (All P < 0.001). Stratified analysis revealed stronger accelerated aging effects in males, smokers, and drinkers. A strengthening trend in the association between DDS and AgeAccel as TDI quartiles increased was noted. ConclusionsThis study suggested that food consumption plays a role in aging process, and adherence to a higher diversity dietary is associated with the slowing down of the aging process.

Prediction of chronological age from resting-state EEG power in the first three years of life.

The infant brain undergoes rapid and significant developmental changes in the first three years of life. Understanding these changes through the prediction of chronological age using neuroimaging data can provide insights into typical and atypical brain development. We utilized longitudinal resting-state EEG data from 457 typically developing infants, comprising 938 recordings, to develop age prediction models. The multilayer perceptron model demonstrated the highest accuracy with an R2 of 0.82 and a mean absolute error of 92.4 days. Aperiodic offset and periodic theta, alpha, and beta power were identified as key predictors of age via Shapley values. Application of the model to EEG data from infants later diagnosed with autism spectrum disorder or Down syndrome revealed significant underestimations of chronological age. This study establishes the feasibility of using EEG to assess brain maturation in early childhood and supports its potential as a clinical tool for early identification of alterations in brain development.

Associations between use of chemical hair products and epigenetic age: Findings from the Sister Study

Background: Hair products may be a source of harmful chemicals and have been linked to age-related health outcomes. We investigated whether the use of hair products is related to epigenetic age in a sample of Black (both Hispanic and non-Hispanic) and non-Hispanic White women. Methods: In a subset of 4358 participants aged 35–74 years from the Sister Study, we estimated cross-sectional associations between self-reported use of four chemical hair products (permanent dye, semipermanent dye, straighteners/relaxers, and hair permanents/body waves) in the year before enrollment (2003–2009) and three DNA methylation-based measures of epigenetic age (DunedinPACE, GrimAge age acceleration [GrimAgeAccel], and PhenoAge age acceleration [PhenoAgeAccel]) using survey-weighted multivariable linear regressions. Associations were estimated both overall and by self-identified race and ethnicity, adjusting for chronological age, socioeconomic and lifestyle factors, body mass index, menopausal status, and DNA methylation platform. Results: Associations between the use of hair products and the three epigenetic age measures were largely null. Use of hair permanents/body waves was modestly associated with higher DunedinPACE among all participants (β ever-never = 0.010; 95% confidence interval [CI] = 0.001, 0.019) and with lower PhenoAgeAccel among Black women (β ever-never = −1.53; 95% CI = −2.84, −0.21). Conclusion: In this US-based study, we found little evidence of associations between chemical hair product use and epigenetic age in Black and non-Hispanic White women. Observed associations were modest and largely not supported by dose–response relationships or were inconsistent across epigenetic age measures. Previously observed associations between chemical hair product use and aging-related health outcomes may not be explained by the biological aging pathways captured by DunedinPACE, GrimAgeAccel, or PhenoAgeAccel. Alternative biological pathways are worth investigating in racially diverse samples.

Routine documentation of pre-treatment functional variables to predict survival in patients on immunotherapy.

e14701 Background: Medical providers often describe concerns about a patient’s functional status in routine clinical documentation (e.g., hard of hearing, recent falls, difficulty with home medication). These clinician-documented pretreatment functional variables (PFVs) may be predictive of outcomes among patients receiving immunotherapy. The goal of this retrospective study is to check for an association between the documentation of PFVs with overall survival (OS), progression-free survival (PFS), and the incidence of immune-related adverse events (irAEs). Methods: We created a retrospective registry of all patients who received at least one dose of an immune checkpoint inhibitor for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center. The investigators created a validated REDCap registry; clinical research specialist at Vasta Global captured most data. PFVs were collected by review of routine clinical documentation 30 days before or after the first dose. Patients were stratified by their number of PFVs (0,1, or 2+) and by their age (≥ or &lt;65 years). PFVs assessed function, nutritional status and social support and were dichotomized to indicate impaired vs not with ten total categories. We used Cox proportional hazard modeling for survival analyses between the three PFV groups, calculated from the first dose of immunotherapy to disease progression, death, and last known follow-up controlling for age, BMI, smoking, and disease type with a two-sided alpha of 0.05. Results: From the overall cohort (n = 3,101), 35% had no PFVs, 32% had one PFV, and 32% had two or more PFVs; 52.5% were considered younger, and 47.5% geriatric-aged (≥65yo). PFVs were more common among the geriatric-aged population (mean 1.43 vs 0.89). The most common cancer types were lung cancer (45%), melanoma (14%), and kidney (6%). The most noted PFVs were visual impairment (26%), unintentional weight loss (22%), inability to walk a quarter block (17%), living alone (16%), and falls (14%). In the overall population, an increasing number of PFVs was associated with shorter OS. When stratified by age, the number of PFVs was associated with shorter progression-free survival (p &lt;0.01) and overall survival (p &lt;0.01) among the geriatric and non-geriatric populations (Table). There was no association between increasing PFVs and incidence of irAEs. Conclusions: Although often considered to be signs of aging, documentation of multiple PFVs was associated with worse OS and PFS among geriatric-aged and non-geriatric-aged populations. This study highlights the utility of routine clinical documentation on health status, including function, nutrition, and social support, to estimate survival regardless of chronologic age. [Table: see text]

Brain Age Gap in Early Illness Schizophrenia and the Clinical High-Risk Syndrome: Associations With Experiential Negative Symptoms and Conversion to Psychosis.

Brain development/aging is not uniform across individuals,spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or agingmap onto specific symptom facets. Using structural MRI, we compared the brain age gap among CHR-P (n = 51), ESZ (n = 78), and unaffected comparison participants (UCP; n = 90), and examined associations with CHR-P psychosis conversion (CHR-P converters n = 10; CHR-P non-converters; n = 23) and positive and negative symptoms. ESZ showed a greater brain age gap relative to UCP and CHR-P (Ps < .010). CHR-P individuals who converted to psychosis showed a greater brain age gap (P = .043) relative to CHR-P non-converters. A larger brain age gap in ESZ was associated with increased experiential (P = .008), but not expressive negative symptom severity. Consistent with schizophrenia pathophysiological models positing abnormal brain maturation, results suggest abnormal brain development is present early in psychosis. An increased brain age gap may be especially relevant to motivational and functional deficits in schizophrenia.

In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth.