Vascular Age

Aging clocks quantify biological aging and help characterize individual health status. What protein interactions are important for accurate aging clocks, and are they zeroth-order or higher-order? Addressing these questions requires learning from large molecular datasets distributed across medical centers, where privacy constraints prevent centralized data sharing. Federated learning offers a natural solution but faces four challenges in this setting: limited local sample sizes, sparse and directional inter-center trust, the need to retain discriminative age prediction while supporting interpretation, and model drift and forgetting under heterogeneous cross-center data. We propose TNFL, a trust-network-based federated learning framework that progressively propagates models along directed pairwise trust relations without centralized aggregation. TNFL combines an age-aware mixture-of-experts model with generative replay to preserve previously learned information and reduce forgetting and drift. Experiments across multiple molecular datasets show that TNFL enables effective aging-clock prediction with limited local data, provides interpretable age-dependent prediction patterns, and maintains stable performance across interaction orders. To investigate the biological questions, we analyze TNFL-identified pairwise protein interactions and their higher-order organization through functional and network analyses. The identified interactions repeatedly form coordinated higher-order subnetworks spanning multiple aging-related biological systems, with several proteins recurring across subnetworks. These findings suggest that TNFL captures molecular relationships beyond isolated pairwise associations and reveals coherent higher-order biological organization associated with aging.

Cultural heritage collections often contain contemporary and historical visual records of the same physical object. Linking these records is difficult because corresponding images may differ in viewpoint, acquisition conditions, color reproduction, framing, resolution, and degradation, while genuine historical images are frequently scarce. This study investigates whether synthetically aged contemporary images can replace or complement missing historical training data in bidirectional instance-level retrieval. Synthetic old-domain images are generated using degradation-oriented transformations. An EfficientNetV2-M model is evaluated on identity-disjoint training, validation, and test sets across three dataset partitions and three training seeds. Mixed real-synthetic training is compared with real-only baselines using proportionally scaled and fixed 300-batch-per-epoch schedules. Complete replacement of genuine historical images reduced bidirectional mean R@1 from 86.56% to 81.27%, showing that synthetic aging does not reproduce the full genuine old-domain variability. Increasing the number of independently generated synthetic variants provided no consistent improvement. Under controlled scarcity, however, synthetic completion improved mean R@1 by 3.69 percentage points at 25% genuine historical coverage and by 2.92 points at 50%, relative to the proportionally scaled real-only baselines. At 75%, the gain decreased to 2.00 points, while performance remained comparable to the complete-real-data reference. Fixed-schedule real-only controls did not reproduce these improvements. The results indicate that genuine and synthetic observations are complementary. Synthetic completion primarily benefits retrieval by extending cross-domain identity coverage rather than by increasing training exposure, with its contribution gradually decreasing as genuine historical coverage increases.

Normative age models are trained to predict chronological age in a nominally healthy cohort. Applied to patients, they deviate, and the gap between predicted and chronological age is read as disease risk. Here, we attribute the disease-related effect size of the age gap directly to individual training samples, rather than using a prediction-level loss as the attribution target. For Cohen's $d$, the resulting closed-form influence functional, validated against leave-one-out retraining, ranks training samples by their effect on held-out case-control separation. Across four diseases and two biomarker modalities in UK Biobank, removing the 10% most influential training samples raises held-out disease-related effect size in every seed. It more than doubles the metabolomic-age effect for type-2 diabetes and raises the brain-age effect for multiple sclerosis by roughly a third. Random removal leaves effect size flat even at 50% removal, confirming the gain comes from which samples are removed, not how many. Flagged subjects carry subclinical cardiometabolic burden that diagnosis-based exclusion misses, on markers the model never sees. For type-2 diabetes, where the method gains most, the marker recovered is HbA1c, the standard measure of blood sugar control. We release pyinfluence, our influence-function package, for reproducibility and reuse.

Arterial pulse waveform morphology evolves with age, reflecting structural and functional changes in the cardiovascular system. Thus, vascular age is a valuable surrogate marker of cardiovascular health, and premature vascular ageing can indicate increased disease risk. Pulse wave analysis could support risk stratification in otherwise asymptomatic adults. We transformed pulse wave time-series data from photoplethysmography (PPG) and arterial tonometry into images, using the Symmetric Projection Attractor Reconstruction (SPAR) method. These SPAR images were used to train a convolutional neural network to classify healthy subjects into two closely spaced age groups (35-40 and 50-55 years). The model demonstrated consistent classification performance across internal and external test sets, achieving F1 scores above 70% for both PPG and tonometry signals. These results suggest that SPAR-derived pulse wave images contain discriminative morphological features even among healthy adults close in age. This proof-of-concept lays the groundwork for future research into the use of SPAR for early risk detection using smart wearables.

Whole-body dual-energy X-ray absorptiometry (DXA) scans are routinely acquired to measure bone density and regional body composition, leaving their spatial structure largely unused. Here, we show that self-supervised learning (SSL) can convert raw DXA images into representations of systemic health. We introduce LeDXA, a vision model based on a joint-embedding predictive architecture (JEPA) that learns by predicting latent representations rather than reconstructing pixels. Trained from scratch on 11,540 unlabeled Human Phenotype Project scans, LeDXA was evaluated internally and on 47,400 external UK Biobank (UKBB) scans. It improved cross-cohort prediction of prevalent diseases and biomarkers beyond scanner-derived DXA measurements and DINOv3, a state-of-the-art general-purpose model, despite approximately 150,000-fold fewer training images and nearly 40-fold fewer parameters. Over a median 4.3-year UKBB follow-up, LeDXA improved incident disease prediction over tabular DXA measures, with the largest gains for hip and knee arthrosis and type 2 diabetes. For hip arthrosis, 66% of incident cases occurred in the highest-risk quartile versus 41% for tabular measures. Its representations predicted chronological age externally (r = 0.88; mean absolute error = 2.90 years), and the biological-age gap tracked broader disease burden and a 45% higher mortality hazard in the oldest-appearing quartile. The gap also decreased in women after starting hormone-replacement therapy, suggesting it may be modifiable. Genome-wide associations recovered mostly known body-composition and bone-density loci, and LeDXA embeddings were more heritable than DINOv3's. These findings reveal prognostic information in DXA images that conventional readouts discard, learnable with relatively little data and modest compute.

DNA methylation (DNAm) serves as one of the most robust molecular biomarkers of biological aging. While conventional epigenetic clocks accurately predict chronological age from high-dimensional CpG profiles, they treat aging as a static regression task, meaning they can only output a single score rather than simulating how an entire profile continuously changes over time. To reconstruct these continuous dynamics, we frame lifelong human epigenetic aging as a trajectory inference problem across discrete age snapshots derived from widely available cross-sectional data. We introduce a two-stage computational pipeline: first, an age-regularized Variational Autoencoder (VAE) maps high-dimensional CpG profiles onto a chronologically ordered latent manifold while preserving a generative decoder bridge back to the original methylation space. Second, we model the continuous movement across this latent space via Regularized Unbalanced Optimal Transport (RUOT) that unifies deterministic drift, random diffusion, and non-conservative mass changes. By resolving this RUOT formulation using the DeepRUOT framework, our model fluidly accommodates population-level density shifts like survivorship bias and cellular attrition without requiring rigid biological priors. Evaluated on a large-scale, 80-year pan-tissue dataset, our model demonstrates robust distribution interpolation and uncovers a prominent late-life surge in the learned growth field that mathematically captures the variance expansion driven by stochastic epigenetic drift. Finally, by decoding continuous latent paths back to individual CpG sites, we reconstruct and empirically verify distinct biological aging archetypes, offering a rigorous, generative paradigm for simulating human molecular aging.

This paper proposes an empirical methodology to study software aging in GPU-based LLM serving systems. Traditional aging studies focus on CPU-centric software with relatively regular workloads; LLM serving is different, spanning a Python host and a CUDA device, handling requests whose cost varies by orders of magnitude, and relying on rapidly evolving software stacks. We run a 216-hour campaign across six co-located deployments under identical stress conditions, monitor host, device, and client metrics in parallel, and apply a statistical pipeline that accounts for autocorrelation and multiple testing. Our results reveal statistically significant memory aging in all deployments, with leak rates strongly dependent on the serving runtime and deployment configuration. Beyond these findings, we provide a reproducible framework that opens a research direction at the intersection of the software aging and rejuvenation and LLM serving communities.

Face aging plays an important role in long-term biometric analysis, cross-age identity verification, and forensic identity analysis. Since the same subject may exhibit multiple plausible appearances at a target age due to genetic, environmental, and lifestyle factors, face aging is inherently a one-to-many generation problem. However, pluralism alone is insufficient for reliable face aging: a model should provide appearance-level candidate diversity within each age group while maintaining sequence-level ordinal reliability across ordered age groups. Existing deterministic aging methods can synthesize visually plausible age-progressed faces, but usually lack stochastic diversity. In contrast, pluralistic aging methods introduce local appearance variations, but often fail to explicitly regulate the identity evolution of the full aging sequence. In this paper, we propose \textbf{DiverAge}, a hierarchical pluralistic face aging framework based on diffusion autoencoding. DiverAge preserves appearance-level diversity through stochastic diffusion decoding and age-conditioned semantic modulation. To improve sequence-level reliability, we introduce a Cross-age Identity Relation Regulator (CARR), an inference-time guidance strategy that jointly denoises multiple target age groups. CARR is guided by a Cross-age Identity Similarity (CIS) prior estimated from real same-identity cross-age pairs, and suppresses excessive cross-age identity drift through one-sided sampling-time guidance without modifying the training objective or introducing extra trainable parameters. Experiments demonstrate that DiverAge improves sequence-level ordinal reliability while maintaining identity preservation, age accuracy, image quality, and appearance-level diversity.

Defining vascular age in terms of physiological function has become one focal point of the extensive studies to categorize and track chronological age. Transcranial Doppler (TCD) is a method by which cerebral blood flow velocity is measured along the major arteries feeding the human brain. This study aims to use features extracted from TCD to estimate chronological age and assess accelerated aging in subjects with various brain diseases. We predict subjects with various brain diseases to present with accelerated cerebrovascular aging when tested on various regression models trained by healthy subjects. 168 healthy subjects and 277 diseased subjects with bilateral TCD recordings of the middle cerebral artery were analyzed using the Morphological Analysis and Clustering of Intracranial Pressure (MOCAIP) algorithm. MOCAIP-generated features and heart rate variability features were used as input features for regression models to predict the brain vascular age. 66 subjects with acute stroke, 27 subjects with post stroke, 26 subjects with Alzheimer's disease, 23 subjects with mild cognitive impairment, and 135 established subjects were tested against the machine learning model to assess for accelerated cerebrovascular age. The trained model, on average, predicted healthy subjects' cerebrovascular age to be 3.69 years above their chronological age. Subjects with different disease conditions exhibited varying levels of age acceleration. The differences in healthy and diseased subjects' performances suggest that features generated using TCD may be relevant when evaluating accelerated cerebrovascular aging. Moreover, imbalanced datasets have been observed to affect the performance of machine-learning-based brain age prediction models.

Epigenetic clocks based on DNA methylation have emerged as powerful tools for estimating biological age, with broad applications in aging research, age-related disease studies, and longevity science. Despite advances across machine learning approaches to epigenetic age prediction, spanning penalised linear regression, deep feedforward networks, residual architectures, and graph neural networks, no existing method jointly models co-methylation graph structure and site-specific DNA sequence context within a unified framework. We propose a unified sequence--graph integration framework for epigenetic age prediction that addresses this gap, integrating eight-dimensional DNA sequence statistical features through a lightweight gated modulation mechanism that adaptively scales each site's methylation signal according to its sequence-determined biological relevance prior to graph convolution. Evaluated on 3,707 blood methylation samples against a comprehensive set of baselines, our method achieves a test MAE of 3.149 years, a 12.8% improvement over the strongest graph-based baseline. Biologically informed statistical features outperform CNN-based sequence encoding, demonstrating that handcrafted sequence features are more effective than end-to-end learned representations in this data regime. Post-hoc interpretability analysis identifies CpG density and local adenine frequency as features with age-dependent importance shifts, consistent with known mechanisms of age-related hypermethylation at CpG-dense promoter regions. Our code is at https://github.com/yaoli2022/graphage-seq.

Aging clocks aim to estimate biological age, a measure of physiological state distinct from chronological age, from observable biomarkers, and are widely used for health assessment and disease analysis. DNA methylation is a particularly informative biomarker due to its stability and strong association with aging, and recent learning-based approaches have improved predictive performance. However, most existing methods treat CpG sites as independent features, overlooking the complex and heterogeneous biological relationships among them. We propose RelAge-GNN, a multi-relational graph neural network framework for DNA methylation-based age prediction. Our method constructs three complementary graphs capturing co-methylation patterns, genomic co-localization, and gene-level associations among CpG sites. Each graph is modeled by an independent GNN branch, and a learnable gating mechanism adaptively fuses the resulting representations. Experiments on large-scale datasets show that RelAge-GNN achieves competitive accuracy and stronger correlation with chronological age compared to state-of-the-art methods. Moreover, the model exhibits improved sensitivity in detecting age acceleration across diverse disease cohorts, highlighting its potential utility for disease characterization. Finally, through post hoc interpretability analyses, we quantify the contributions of different relational structures and CpG sites, providing biologically meaningful insights and suggesting potential directions for aging-related research. Our code is available at: https://anonymous.4open.science/r/RelAge-GNN-F1E3/.

Recovering 3D human pose and shape from a single image remains a cornerstone of human-centric vision, yet most methods assume adult subjects and optimize each person independently. These assumptions fail in real-world, all-age scenes, where body proportions and depth must be resolved jointly. We introduce Anny-Fit, a multi-person, camera-space optimization framework for all-age 3D human mesh recovery (HMR). Unlike existing per-person fitting methods, Anny-Fit jointly optimizes all individuals directly in the camera coordinate system, enforcing global spatial consistency. At the core of our approach is the use of multiple forms of expert knowledge -- including metric depth maps, instance segmentation, 2D keypoints, and, VLM-derived semantic attributes such as age and gender -- each obtained from dedicated off-the-shelf networks. These complementary signals jointly guide the optimization, constraining the depth-scale ambiguity characteristic of all-age scenes. Across diverse datasets, Anny-Fit consistently improves 2D reprojection accuracy (+13 to 16), relative depth ordering (+6 to 7), 3D estimation error (-9 to -29) and shape estimation (+25 to +82), producing more coherent scenes. Finally, we show that VLM-based semantic knowledge can be distilled into an HMR model via the pseudo-ground-truth annotations produced by Anny-Fit on training data, enabling it to learn semantically meaningful shape parameters while improving HMR performance. Our approach bridges adult-only and all-age modeling by enabling zero-shot adaptation of adult-trained HMR pipelines to the full age spectrum without retraining. Code is publicly available at https://github.com/naver/anny-fit.

Electrocardiogram (ECG) biometrics have emerged as a promising modality for continuous, liveness-aware authentication in wearable systems. However, many prior studies report overly optimistic results due to data leakage (e.g., random splits within the same session). To address this issue, we introduce ECG-biometrics-bench, a modular, reproducible benchmarking framework that standardizes preprocessing, segmentation, and evaluation across seven widely used public ECG datasets spanning clinical, ambulatory, and large-scale cohort settings. The framework supports both closed-set and open-set (i.e., subject-disjoint generalization in this work) evaluation, as well as progressively realistic protocols including cross-session and long-term temporal separation. To facilitate reproducible research in the community, the ECG-biometrics-bench repository will be made publicly accessible on GitHub upon the acceptance of this manuscript. Through a comprehensive multi-dataset analysis, we expose the Random Split Fallacy, demonstrating that intra-session evaluation protocols artificially inflate performance while masking severe degradation caused by temporal drift and unseen identities. Furthermore, by evaluating multiple architectures, including DeepECG, ResNet1D, and CNN-LSTM, we show that these failures are not model-specific but are likely inherent to current supervised feature-learning paradigms. Finally, we demonstrate that performance degradation due to temporal aging can be partially mitigated through a heavy enrollment, lightweight authentication strategy based on dynamic multi-session template fusion. These findings establish a more realistic baseline for ECG biometrics and highlight critical challenges that must be addressed for reliable real-world deployment.

Large Language Model (LLM)-based agents exhibit systemic failures in compositional generalization, limiting their robustness in interactive environments. This work introduces AGEL-Comp, a neuro-symbolic AI agent architecture designed to address this challenge by grounding actions of the agent. AGEL-Comp integrates three core innovations: (1) a dynamic Causal Program Graph (CPG) as a world model, representing procedural and causal knowledge as a directed hypergraph; (2) an Inductive Logic Programming (ILP) engine that synthesizes new Horn clauses from experiential feedback, grounding symbolic knowledge through interaction; and (3) a hybrid reasoning core where an LLM proposes a set of candidate sub-goals that are verified for logical consistency by a Neural Theorem Prover (NTP). Together, these components operationalize a deduction--abduction learning cycle: enabling the agent to deduce plans and abductively expand its symbolic world model, while a neural adaptation phase keeps its reasoning engine aligned with new knowledge. We propose an evaluation protocol within the \texttt{Retro Quest} simulation environment to probe for compositional generalization scenarios to evaluate our AGEL agent. Our findings clearly indicate the better performance of our AGEL model over pure LLM-based models. Our framework presents a principled path toward agents that build an explicit, interpretable, and compositionally structured understanding of their world.