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A 70-year-old leukemia drug is still revealing new secrets. Researchers found that removing a protein called NUDT5 protected cells from the drug, even though simply blocking the protein had little effect. The unexpected result points to a hidden cellular role that could help explain why people respond differently to certain leukemia treatments.

A newly identified breakdown in communication between nerves and muscles could help explain why people lose strength as they age. Researchers were able to improve muscle strength in an animal model by targeting a key protein, raising hopes that some age-related weakness could eventually be treated.

Alzheimer disease begins in the brain many years before symptoms, but early changes are usually studied after death or indirectly through fluid and imaging biomarkers. Here we show that small brain biopsies collected during ventriculoperitoneal shunt surgery can be used to study Alzheimer disease pathology and protein turnover during life. We analysed biopsies from 18 individuals with suspected normal pressure hydrocephalus, alongside matched ventricular and lumbar cerebrospinal fluid and...

Retinal fundus images offer a non-invasive window into systemic aging. Here, we fine-tune a foundation model (RETFound) to predict chronological age from color fundus images in 71,343 participants from the UK Biobank, achieving a mean absolute error of 2.85 years. The resulting retinal age gap, i.e. the difference between predicted and chronological age, is associated with cardiometabolic traits, inflammation, cognitive performance, all-cause mortality, dementia, cancer, and incident...

Epigenetic aging is a hallmark of chronic diseases. While such epigenetic changes can arise following tissue injury, the cell types most affected remain largely unknown. Here we built a cross-species single-cell multiomics atlas of DNA methylation, chromatin accessibility and transcription profiles from healthy, injured (human) and aged (mouse) kidneys. We found that tubular epithelial cells in diseased kidneys exhibit pronounced accelerated epigenetic aging and showed that this pathological...

Aging is accompanied by progressive physiological decline, yet the microbiome determinants that modulate aging remain unclear. Here, we identify Neisseria flavescens (Nf) as an oral commensal associated with decelerated aging in humans. Using AURORA, a generative multi-modality framework, we developed multi-modality aging clocks, performed in silico screening for age-gap-reducing interventions and predicted Nf as a top hit. In silico perturbations linked increased Nf abundance to favorable...

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Cerebrovascular disease is a major but poorly understood feature of Alzheimer's disease (AD). The strongest genetic AD risk factor, apolipoprotein E4 (APOE4), is associated with cerebrovascular degeneration, including vascular amyloid deposition and fibrosis. To uncover how APOE4 promotes cerebrovascular pathology, we assembled a single-cell transcriptomic atlas of human brain vasculature. In APOE4 carriers, pericyte abundance was significantly reduced and accompanied by the emergence of a...

Early diagnosis of Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI), requires efficient computational frameworks capable of handling high-dimensional and large-scale 18F-FDG-PET data. To address challenges in feature redundancy and computational efficiency, we propose a unified framework integrating an enhanced Grey Wolf Optimizer (CDL-GWO) with approximate nearest neighbor search based on Facebook AI Similarity Search (FAISS). The proposed CDL-GWO incorporates...

The "healthy drinking" paradox refers to situations where alcohol consumption is misleadingly associated with better health outcomes, a pattern frequently observed in observational studies that are prone to a range of confounding factors. Some recent studies developing organ-specific proteomic aging clocks report that alcohol consumption is linked to slower aging in select organs, even as it accelerates aging in others, thus echoing this paradox, with substantial discrepancies across such...

Cardiovascular health, depressive symptoms, and cognitive performance are closely interconnected and jointly influence all-cause mortality. We investigated the independent associations of Life's Simple 7 (LS7), depressive symptom trajectories, and cognitive performance with all-cause mortality and conducted exploratory four-way decomposition analyses to evaluate complementary mechanistic hypotheses linking these factors. We analyzed data from the Healthy Aging in Neighborhoods of Diversity...

Perovskite photovoltaics are limited by structural instabilities initiated during crystallization and amplified under operation. We report that a lattice-matched Prussian blue scaffold directs heterogeneous nucleation to produce highly oriented, strain-relaxed films. Its redox-active Fe-C≡N-Fe network mediates the conversion of Pb⁰ and I⁰ defects, and its rigid open framework suppresses A-site cation redistribution and the resulting electronic inhomogeneity under bias. This strategy yielded...

Infant macaques showed immune changes and signs of faster aging years after inhaling smoke.

Fibrotic remodeling of tissues and tumors establishes immunosuppressive microenvironments that drive organ dysfunction and, in cancer, limit response to immunotherapy. Senescent-like cells are conserved drivers of fibrosis and therapeutic targets, yet their functional heterogeneity complicates therapeutic intervention. Here, we show that P-selectin is expressed by a subset of senescent-like cells in fibrotic tissues and tumors. Leveraging fucoidan-based nanoparticles that bind P-selectin, we...

Targeting senescence decreases fibrosis and boosts the response of cancer cells to immunotherapy.

Although cortical thinning and atrophy are well documented in aging and neurodegenerative disease, the cortical structural features associated with preserved or superior cognition across typical adulthood remain incompletely characterized. We examined associations between cortical thickness and cognitive performance in a large, typically aging cohort and tested whether they vary by age and cognitive domain. We analyzed cross-sectional data from cognitively healthy adults in the Human Connectome...

CONCLUSIONS: A machine learning-derived CFI integrating diagnoses, medications, and procedures demonstrated robust prediction of mortality and other adverse outcomes, supporting its incremental value in population-based frailty assessment.

Wearable devices offer the ability to objectively characterize free-living physical activity; however, raw step-count data generated by commercial devices require systematic processing before they can support rigorous inference. We describe a transparent, reproducible standard operating procedure (SOP) for transforming epoch-level step-count data from commercial Garmin devices into participant-level analytic variables and demonstrate its application in the STRRIDE-PD Reunion study: a long-term...

CONCLUSION: Midlife MetS was associated with modest reductions in within-network DMN connectivity, with abdominal obesity and low HDL cholesterol as the primary contributing MetS components. Reduced DMN connectivity was associated with poorer verbal fluency performance. These findings suggest that subtle differences in higher-order functional brain network organization associated with metabolic syndrome can be detected during midlife and are related to cognitive functioning, highlighting the...