Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Targeting mitochondria for ovarian aging: new insights into mechanisms and therapeutic potential.

Ovarian aging is a complex process characterized by a decline in oocyte quantity and quality, directly impacting fertility and overall well-being. Recent researches have identified mitochondria as pivotal players in the aging of ovaries, influencing various hallmarks and pathways governing this intricate process. In this review, we discuss the multifaceted role of mitochondria in determining ovarian fate, and outline the pivotal mechanisms through which mitochondria contribute to ovarian aging. Specifically, we emphasize the potential of targeting mitochondrial dysfunction through innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, mitochondrial transfer, and traditional Chinese medicine. These strategies hold promise as effective means to mitigate age-related fertility decline and preserve ovarian health. Drawing insights from advanced researches in the field, this review provides a deeper understanding of the intricate interplay between mitochondrial function and ovarian aging, offering valuable perspectives for the development of novel therapeutic interventions aimed at preserving fertility and enhancing overall reproductive health.

[The relationship between intraocular pressure and age-related variations in ocular rigidity]. / Vzaimosvyaz' vnutriglaznogo davleniya s involyutsionnymi kolebaniyami rigidnosti glaza.

PURPOSE: This study aimed to identify the correlation between age-related fluctuations in the average values of rigidity of the fibrous tunic of the eye (FTE) and corresponding ranges of true intraocular pressure (IOP) in healthy eyes and eyes with open-angle glaucoma (OAG); using the identified ranges of FTE rigidity, to establish the appropriate IOP zones for healthy and glaucomatous eyes, taking into account the aging periods as classified by the World Health Organization (WHO). MATERIAL AND METHODS: Ocular-Response Analyzer tonometry was used according to the Koshits-Svetlova dynamic diagnostic method to examine 674 patients with healthy eyes and 518 patients with glaucomatous eyes, aged 18 to 90 years, classified according to the WHO aging periods, and a theoretical analysis was conducted to estimate clinical values of FTE rigidity, the current level of true IOP, and the calculated individual IOP level in a patient's eye during youth. RESULTS: The following IOP level zones were identified for patients with healthy and glaucomatous eyes: low IOP zone (≤13 mm Hg); medium IOP zone (14-20 mm Hg); elevated IOP zone (21-26 mm Hg); high IOP zone (27-32 mm Hg); subcompensated IOP zone (33-39 mm Hg); and decompensated IOP zone (≥40 mm Hg). CONCLUSION: The fundamental physiological criterion "rigidity" does not depend on central corneal thickness and consistently reflects the current level of true IOP. In all examined patients, both with healthy and glaucomatous eyes, healthy and glaucoma eyes with the same level of current rigidity had the same level of IOP. The ability to assign a given healthy or glaucomatous eye to a specific individual IOP zone is particularly important for the polyclinic system.

Aperiodic component of EEG power spectrum and cognitive performance are modulated by education in aging.

Recent studies have shown a growing interest in the so-called "aperiodic" component of the EEG power spectrum, which describes the overall trend of the whole spectrum with a linear or exponential function. In the field of brain aging, this aperiodic component is associated both with age-related changes and performance on cognitive tasks. This study aims to elucidate the potential role of education in moderating the relationship between resting-state EEG features (including aperiodic component) and cognitive performance in aging. N = 179 healthy participants of the "Leipzig Study for Mind-Body-Emotion Interactions" (LEMON) dataset were divided into three groups based on age and education. Older adults exhibited lower exponent, offset (i.e. measures of aperiodic component), and Individual Alpha Peak Frequency (IAPF) as compared to younger adults. Moreover, visual attention and working memory were differently associated with the aperiodic component depending on education: in older adults with high education, higher exponent predicted slower processing speed and less working memory capacity, while an opposite trend was found in those with low education. While further investigation is needed, this study shows the potential modulatory role of education in the relationship between the aperiodic component of the EEG power spectrum and aging cognition.

Multispectral label-free in vivo cellular imaging of human retinal pigment epithelium using adaptive optics fluorescence lifetime ophthalmoscopy improves feasibility for low emission analysis and increases sensitivity for detecting changes with age and eccentricity.

Significance: Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) provides a label-free approach to observe functional and molecular changes at cellular scale in vivo. Adding multispectral capabilities improves interpretation of lifetime fluctuations due to individual fluorophores in the retinal pigment epithelium (RPE). Aim: To quantify the cellular-scale changes in autofluorescence with age and eccentricity due to variations in lipofuscin, melanin, and melanolipofuscin in RPE using multispectral AOFLIO. Approach: AOFLIO was performed on six subjects at seven eccentricities. Four imaging channels ( λ ex / λ em ) were used: 473/SSC, 473/LSC, 532/LSC, and 765/NIR. Cells were segmented and the timing signals of each pixel in a cell were combined into a single histogram, which were then used to compute the lifetime and phasor parameters. An ANOVA was performed to investigate eccentricity and spectral effects on each parameter. Results: A repeatability analysis revealed < 11.8 % change in lifetime parameters in repeat visits for 532/LSC. The 765/NIR and 532/LSC had eccentricity and age effects similar to previous reports. The 473/LSC had a change in eccentricity with mean lifetime and a phasor component. Both the 473/LSC and 473/SSC had changes in eccentricity in the short lifetime component and its relative contribution. The 473/SSC had no trend in eccentricity in phasor. The comparison across the four channels showed differences in lifetime and phasor parameters. Conclusions: Multispectral AOFLIO can provide a more comprehensive picture of changes with age and eccentricity. These results indicate that cell segmentation has the potential to allow investigations in low-photon scenarios such as in older or diseased subjects with the co-capture of an NIR channel (such as 765/NIR) with the desired spectral channel. This work represents the first multispectral, cellular-scale fluorescence lifetime comparison in vivo in the human RPE and may be a useful method for tracking diseases.

Age-related changes in cheek skin movement: A case study of Japanese women.

BACKGROUND: The majority of conventional studies on skin aging have focused on static conditions. However, in daily life, the facial skin we encounter is constantly in motion due to conversational expressions and changes in facial expressions, causing the skin to alter its position and shape, resulting in a dynamic state. Consequently, it is hypothesized that characteristics of aging not apparent in static conditions may be present in the dynamic state of the skin. Therefore, this study investigates age-related changes in dynamic skin characteristics associated with facial expression alterations. METHODS: A motion capture system measured the dynamic characteristics (delay and stretchiness of skin movement associated with expression) of the cheek skin in response to facial expressions among 86 Japanese women aged between 20 and 69 years. RESULTS: The findings revealed an increase in the delay of cheek skin response to facial expressions (r = 0.24, p < 0.05) and a decrease in the stretchiness of the lower cheek area with age (r = 0.60, p < 0.01). An increasing variance in delay and stretchiness within the same age group was also observed with aging. CONCLUSION: The findings of this study revealed that skin aging encompasses both static characteristics, such as spots, wrinkles, and sagging, traditionally studied in aging research, and dynamic aging characteristics of the skin that emerge in response to facial expression changes. These dynamic aging characteristics could pave the way for the development of new methodologies in skin aging analysis and potentially improve our understanding and treatment of aging impressions that are visually perceptible in daily life but remain unexplored.

Locus coeruleus contrast and diffusivity metrics differentially relate to age and memory performance.

Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for all imaging modalities interacted with sex, with larger age group differences in males than females for MTC and NODDI metrics. Age group differences also varied across locus coeruleus subdivision for DTI and NODDI metrics, and across locus coeruleus hemispheres for MTC. Within older adults, however, there were no significant effects of age on MTC or DTI metrics, only an interaction between age and sex for free diffusion. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, inclusion of DTI and NODDI metrics, and breakdowns by locus coeruleus subdivision and hemisphere make important and novel contributions to our understanding of the aging of locus coeruleus structure.

Persistent vocal learning in an aging open-ended learner reflected in neural FoxP2 expression.

BACKGROUND: Most vocal learning species exhibit an early critical period during which their vocal control neural circuitry facilitates the acquisition of new vocalizations. Some taxa, most notably humans and parrots, retain some degree of neurobehavioral plasticity throughout adulthood, but both the extent of this plasticity and the neurogenetic mechanisms underlying it remain unclear. Differential expression of the transcription factor FoxP2 in both songbird and parrot vocal control nuclei has been identified previously as a key pattern facilitating vocal learning. We hypothesize that the resilience of vocal learning to cognitive decline in open-ended learners will be reflected in an absence of age-related changes in neural FoxP2 expression. We tested this hypothesis in the budgerigar (Melopsittacus undulatus), a small gregarious parrot in which adults converge on shared call types in response to shifts in group membership. We formed novel flocks of 4 previously unfamiliar males belonging to the same age class, either "young adult" (6 mo - 1 year) or "older adult" (≥ 3 year), and then collected audio-recordings over a 20-day learning period to assess vocal learning ability. Following behavioral recording, immunohistochemistry was performed on collected neural tissue to measure FoxP2 protein expression in a parrot vocal learning center, the magnocellular nucleus of the medial striatum (MMSt), and its adjacent striatum. RESULTS: Although older adults show lower vocal diversity (i.e. repertoire size) and higher absolute levels of FoxP2 in the MMSt than young adults, we find similarly persistent downregulation of FoxP2 and equivalent vocal plasticity and vocal convergence in the two age cohorts. No relationship between individual variation in vocal learning measures and FoxP2 expression was detected. CONCLUSIONS: We find neural evidence to support persistent vocal learning in the budgerigar, suggesting resilience to aging in the open-ended learning program of this species. The lack of a significant relationship between FoxP2 expression and individual variability in vocal learning performance suggests that other neurogenetic mechanisms could also regulate this complex behavior.

Inequalities in health-related quality of life and functional health of an aging population: A Canadian community perspective.

BACKGROUND: Reducing health inequalities among older adults is crucial to ensuring healthy aging is within reach for all. The current study provides a timely update on demographic- and geographic-related inequalities in healthy aging among older adults residing in Canadian communities. METHODS: Data was extracted from the Canadian Health Survey on Seniors [2019-2020] for ~6 million adults aged 65 years and older residing in 10 provinces of Canada. Healthy aging was defined by two indices: 1] health-related quality of life and 2] functional health. Poisson regression models and spatial mapping were used to demonstrate inequalities among age, race, and sex categories, and health regions. RESULTS: Approximately 90.3% of individuals reported less than perfect quality of life and 18.8% reported less than perfect functional health. The prevalence of less than perfect quality of life was higher for females [PR 1.14, 95% CI;1.02-1.29] and for older adults aged ≥80 years as compared to males and older adults aged ≤79 years [PR 1.66, 95% CI;1.49-1.85]. Similarly, the prevalence of less than perfect functional health was higher for females [PR 1.58, 95% CI;1.32-1.89] and for older adults aged ≥80 years [PR 2.71, 95% CI;2.59-2.84]. Spatial mapping showed that regions of lower quality of life were concentrated in the Prairies and Western Ontario, whereas regions of higher quality of life were concentrated in Quebec. CONCLUSIONS: Amongst older individuals residing in Canadian communities, less than perfect quality of life and functional health is unequally distributed among females, older adults aged ≥80 years, and those residing in the Prairie regions specifically. Newer policy should focus on interventions targeted at these subpopulations to ensure that healthy aging in within reach for all Canadians.

Attenuation and distortion components of age-related hearing loss: Contributions to recognizing temporal-envelope filtered speech in modulated noise.

Older adults with hearing loss may experience difficulty recognizing speech in noise due to factors related to attenuation (e.g., reduced audibility and sensation levels, SLs) and distortion (e.g., reduced temporal fine structure, TFS, processing). Furthermore, speech recognition may improve when the amplitude modulation spectrum of the speech and masker are non-overlapping. The current study investigated this by filtering the amplitude modulation spectrum into different modulation rates for speech and speech-modulated noise. The modulation depth of the noise was manipulated to vary the SL of speech glimpses. Younger adults with normal hearing and older adults with normal or impaired hearing listened to natural speech or speech vocoded to degrade TFS cues. Control groups of younger adults were tested on all conditions with spectrally shaped speech and threshold matching noise, which reduced audibility to match that of the older hearing-impaired group. All groups benefitted from increased masker modulation depth and preservation of syllabic-rate speech modulations. Older adults with hearing loss had reduced speech recognition across all conditions. This was explained by factors related to attenuation, due to reduced SLs, and distortion, due to reduced TFS processing, which resulted in poorer auditory processing of speech cues during the dips of the masker.

Social Media Programs for Outreach and Recruitment Supporting Aging and Alzheimer Disease and Related Dementias Research: Longitudinal Descriptive Study.

BACKGROUND: Social media may be a useful method for research centers to deliver health messages, increase their visibility in the local community, and recruit study participants. Sharing examples of social media-based community outreach and educational programs, and evaluating their outcomes in this setting, is important for understanding whether these efforts have a measurable impact. OBJECTIVE: The aim of this study is to describe one center's social media activities for community education on topics related to aging, memory loss, and Alzheimer disease and related dementias, and provide metrics related to recruitment into clinical research studies. METHODS: Several social media platforms were used, including Facebook, X (formerly Twitter), and YouTube. Objective assessments quantified monthly, based on each platform's native dashboard, included the number of followers, number of posts, post reach and engagement, post impressions, and video views. The number of participants volunteering for research during this period was additionally tracked using a secure database. Educational material posted to social media most frequently included content developed by center staff, content from partner organizations, and news articles or resources featuring center researchers. Multiple educational programs were developed, including social media series, web-based talks, Twitter chats, and webinars. In more recent years, Facebook content was occasionally boosted to increase visibility in the local geographical region. RESULTS: Up to 4 years of page metrics demonstrated continuing growth in reaching social media audiences, as indicated by increases over time in the numbers of likes or followers on Facebook and X/Twitter and views of YouTube videos (growth trajectories). While Facebook reach and X/Twitter impression rates were reasonable, Facebook engagement rates were more modest. Months that included boosted Facebook posts resulted in a greater change in page followers and page likes, and higher reach and engagement rates (all P≤.002). Recruitment of participants into center-affiliated research studies increased during this time frame, particularly in response to boosted Facebook posts. CONCLUSIONS: These data demonstrate that social media activities can provide meaningful community educational opportunities focused on Alzheimer disease and related dementias and have a measurable impact on the recruitment of participants into research studies. Additionally, this study highlights the importance of tracking outreach program outcomes for evaluating return on investment.

Infertility problems in the context of reproductive ageing.

The article evaluates the prevalence of infertility problems in the Czech population, identifies methods used by individuals or couples attempting to achieve pregnancy and evaluates in more detail the use of assisted reproduction technology (ART) in contemporary Czech society. The results show that 27% of women and men in their forties declare they have experienced a time when they were trying to get pregnant but did not conceive within at least 12 months. In the general population of reproductive age, one in five declares experience with methods helping to get pregnant. Methods that do not require a doctor's visit are the most frequently used (one in ten declare monitoring ovulation), and 5% of the general population have experience of ART. Among those who have experienced some period of infertility, the experience of methods to assist conception is significantly higher (3/4 of men and 2/3 of women), and the use of medically assisted reproduction is also higher (a quarter have experience of taking medication and a quarter of assisted reproduction).

Self-perceptions of aging, physical activity, and depressive symptoms in older community residents with varied neighborhood walkability in Taiwan.

BACKGROUND: Prior research has identified the mediating effect of physical activity in the relationship between self-perceptions of aging and physical health. However, this impact on mental health is unknown, and the influence of environmental contexts proposed by ecological models in this regard remains largely unexplored. Therefore, this study aimed to investigate the role of physical activity in the relationship between self-perceptions of aging and depressive symptoms in older adults, and compare the impact across four levels of neighborhood walkability. METHODS: A sample of 1,055 community-dwelling older adults aged 65 or above was obtained through random-digit-dialing computer-assisted telephone interviewing. The individual's neighborhood walkability was calculated using Walk Score®, and categorized into four levels: car-dependent, somewhat walkable, very walkable, and walker's paradise. Partial least squares structural equation modelling was employed. RESULTS: We found that more positive self-perceptions of aging were associated with fewer depressive symptoms and a mediation effect of physical activity in this relationship. Among the four levels of neighborhood walkability, the mediation effect of physical activity was only statistically significant in the lowest level (car-dependent). The findings supported our hypotheses regarding the mediating effect of self-perceptions of aging on depressive symptoms via physical activity. Neighborhood walkability might potentially influence the mediating role of physical activity. CONCLUSIONS: This study emphasizes key areas on intervention programs and policy formulation to promote mental health in older adults.

The association between SII and aging: evidence from NHANES 1999-2018.

Background: The study aimed to examine the association between the systemic immune-inflammation index (SII), a contemporary metric of systemic inflammatory response, and biological aging, which are closely interconnected processes. Methods: This cross-sectional study utilized 10 cycles of data from the NHANES database spanning from 1990 to 2018. The study examined the relationship between the SII index, calculated as P * N/L, where P represents preoperative peripheral platelet count, N represents neutrophil count, and L represents lymphocyte count, and biological aging. Biological aging was assessed through various methods, such as phenotypic age, phenotypic age acceleration (PhenoAgeAccel), biological age, and biological age acceleration (BioAgeAccel). Correlations were analyzed using weighted linear regression and subgroup analysis. Results: Among the 7,491 participants analyzed, the average age was 45.26 ± 0.34 years, with 52.16% being female. The average phenotypic and biological ages were 40.06 ± 0.36 and 45.89 ± 0.32 years, respectively. Following adjustment for potential confounders, elevated SII scores were linked to increased phenotypic age, biological age, Phenotypic age acceleration, and Biological age acceleration. Positive correlations were observed between health behavior and health factor scores and biological aging, with stronger associations seen for health factors. In health factor-specific analyses, the ß coefficient was notably higher for high BMI. The robust positive associations between SII scores and both phenotypic age and biological age in the stratified analyses were consistently observed across all strata. Conclusion: The evidence from the NHANES data indicate that SII may serve as a valuable marker for assessing different facets of aging and health outcomes, such as mortality and the aging process. Additional research is warranted to comprehensively elucidate the implications of SII in the aging process and its utility as a clinical instrument for evaluating and addressing age-related ailments.

Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis.

Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

Association between Resting Heart Rate and Machine Learning-Based Brain Age in Middle- and Older-Age.

BACKGROUND: Resting heart rate (RHR), has been related to increased risk of dementia, but the relationship between RHR and brain age is unclear. OBJECTIVE: We aimed to investigate the association of RHR with brain age and brain age gap (BAG, the difference between predicted brain age and chronological age) assessed by multimodal Magnetic Resonance Imaging (MRI) in mid- and old-aged adults. DESIGN: A longitudinal study from the UK Biobank neuroimaging project where participants underwent brain MRI scans 9+ years after baseline. SETTING: A population-based study. PARTICIPANTS: A total of 33,381 individuals (mean age 54.74 ± 7.49 years; 53.44% female). MEASUREMENTS: Baseline RHR was assessed by blood pressure monitor and categorized as <60, 60-69 (reference), 70-79, or ≥80 beats per minute (bpm). Brain age was predicted using LASSO through 1,079 phenotypes in six MRI modalities (including T1-weighted MRI, T2-FLAIR, T2*, diffusion-MRI, task fMRI, and resting-state fMRI). Data were analyzed using linear regression models. RESULTS: As a continuous variable, higher RHR was associated with older brain age (ß for per 1-SD increase: 0.331, 95% [95% confidence interval, CI]: 0.265, 0.398) and larger BAG (ß: 0.263, 95% CI: 0.202, 0.324). As a categorical variable, RHR 70-79 bpm and RHR ≥80 bpm were associated with older brain age (ß [95% CI]: 0.361 [0.196, 0.526] / 0.737 [0.517, 0.957]) and larger BAG (0.256 [0.105, 0.407] / 0.638 [0.436, 0.839]), but RHR< 60 bpm with younger brain age (-0.324 [-0.500, -0.147]) and smaller BAG (-0.230 [-0.392, -0.067]), compared to the reference group. These associations between elevated RHR and brain age were similar in both middle-aged (<60) and older (≥60) adults, whereas the association of RHR< 60 bpm with younger brain age and larger BAG was only significant among middle-aged adults. In stratification analysis, the association between RHR ≥80 bpm and older brain age was present in people with and without CVDs, while the relation of RHR 70-79 bpm to brain age present only in people with CVD. CONCLUSION: Higher RHR (>80 bpm) is associated with older brain age, even among middle-aged adults, but RHR< 60 bpm is associated with younger brain age. Greater RHR could be an indicator for accelerated brain aging.