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Aging is the primary risk factor for chronic disease and is characterized by profound structural and architectural remodeling of human tissues. Here, we present a comprehensive assessment of these changes using 25,712 whole-slide histopathological images from 40 tissue types across 983 individuals in the Genotype-Tissue Expression cohort. By leveraging deep learning, we quantified nuanced morphological alterations to develop 'tissue clocks', predictors of biological age that reflect tissue...

Spontaneous intracerebral hemorrhage (ICH) is a highly lethal and disabling form of stroke, in which hematoma expansion (HE) is a major and potentially modifiable determinant of early neurological deterioration and poor functional outcome. Computed tomography (CT) remains the first-line imaging modality for acute ICH and provides essential information for early HE risk stratification. However, current evidence is dispersed across conventional CT signs, composite scores, radiomics, machine...

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular...

CONCLUSIONS: Exercise improves balance, but modality choice should consider balance domain. Current estimates were most favourable for perturbation training in overall and static balance under supervision, sensory training at home, Tai Chi in global balance, Pilates in dynamic balance, and agility stepping or aquatic exercise in proactive balance. These estimates do not establish superiority. Dose should reflect task-specific challenge, safety and feasibility, because METs capture metabolic cost...

CONCLUSION: Moderate levels of green and blue spaces were associated with lower levels of biological aging. Nonlinear associations were stronger in socially vulnerable groups, suggesting that equitable nature-based planning could be a strategic public health intervention to promote healthy aging.

Graph theory provides unique tools to assess complex networks. It has been previously used with functional magnetic resonance imaging (fMRI) datasets to quantify macroscopic-scale connections among different brain regions, readily capturing brain network changes in subjects with Alzheimer's disease. Here, we apply graph theory to miniscope calcium imaging data recorded from the prefrontal cortex of freely behaving wild-type (WT) and Shank3^(fx) mice (a mouse model of autism) during social...

The choroid plexus (ChP) regulates cerebrospinal fluid homeostasis and immune surveillance, but its cellular organization and response to Alzheimer's disease (AD) remain incompletely defined. Here, we integrate single-nucleus RNA sequencing with spatial transcriptomics to generate a high-resolution atlas of the adult human ChP. We identify all major epithelial, stromal, and immune populations and resolve heterogeneity within macrophages, including a distinct subset expressing the giant protein...

Social interaction regulates neuronal excitability and behavior, and the lateral septum (LS) plays an important role in social behavior. However, the molecular mechanisms that support LS-dependent social responses remain unclear. Here, we show that neuronal activity-driven glucose transporter 4 (GLUT4) plasma translocation in LS GABAergic neurons supports social familiarity. Neuronal activation triggers CaMKIIα-mediated phosphorylation of GLUT4 at Ser243 and Ser254, which enhances Rab10 binding,...

The integrated stress response (ISR) enables cells to adapt to diverse cellular stresses, but during chronic or unresolved stress it becomes maladaptive and is implicated in neurodegenerative diseases, including Parkinson disease (PD). The mechanisms underlying maladaptive ISR-driven neurodegeneration, however, remain poorly defined. Here, we find a critical pathway by which chronic ISR activation promotes neurodegeneration in neurotoxin and α synucleinopathy models of PD in vitro and in vivo....

Gamma wave entrainment is a promising approach for improving cognitive function, particularly in the early stages of Alzheimer's disease. However, for everyday treatment, a light source system that maintains visibility while delivering effective stimulation is essential for patient comfort and practicality. To address this need, we developed organic light-emitting diode (OLED) glasses with optimized large-area transparent OLEDs for gamma wave entrainment. The optimization involved all layers of...

The choroid plexus (ChP) regulates cerebrospinal fluid homeostasis and immune surveillance, but its cellular organization and response to Alzheimer's disease (AD) remain incompletely defined. Here, we integrate single-nucleus RNA sequencing with spatial transcriptomics to generate a high-resolution atlas of the adult human ChP. We identify all major epithelial, stromal, and immune populations and resolve heterogeneity within macrophages, including a distinct subset expressing the giant protein...

Perovskite solar cells (PSCs) using self-assembled monolayers (SAMs) as hole transporting materials have achieved impressive efficiencies. However, the vulnerability of SAMs causes desorption under light and thermal stress. While various modifications to the conjugated core and anchoring group of SAMs have been explored, challenges in balancing efficiency and stability remain. Here, we introduce a new class of cross-linkable SAMs, uniquely functionalized at the molecular linker. Upon in situ...

In Alzheimer's disease, the protein tau is thought to redistribute from axons to the somatodendritic compartment and form fibrillar aggregates. Although tau aggregation is a hallmark of Alzheimer's disease, the dynamics of its synthesis and degradation are not well characterized. Given that nascent polypeptides are particularly susceptible to misfolding, local control of tau synthesis and degradation may be essential to prevent aggregation. Here we develop STARFISH, a method for visualizing the...

Aging-related metabolic decline, particularly impaired glucose tolerance, represents a growing challenge in aging populations. Probiotics are promising modulators of host metabolism; however, how sex differences influence their efficacy in mitigating metabolic aging remains poorly understood. Here, we administered Lactiplantibacillus plantarum AS21 to naturally aged male and female mice for 6 months. We observed a pronounced sexual dimorphism in metabolic decline, with aged males exhibiting more...

CONCLUSIONS: Storey configuration and number of transition points constitute structural conditions that shape outdoor access in RCFs. These findings have implications for age-friendly design and planning of RCFs as well as for person-centred care and rehabilitation.

Endolysosomal membranes are frequently damaged by pathogenic stress associated with aging, infection, and neurodegeneration, and failure to repair such damage leads to inflammation and cell death. Recent advances identify membrane ATG8 conjugation (atg8ylation) as a key process that links damage detection to coordinated lysosomal repair, removal, and regeneration. Beyond its canonical role in macroautophagy, membrane atg8ylation also occurs on preexisting, non-autophagosomal single membranes...

CONCLUSION: Commonly used claims-based algorithms to identify ADRD had reasonable validity, though each presented important context-dependent tradeoffs and none was uniformly superior. These findings highlight the importance of accurately diagnosing ADRD in clinical settings and of understanding each algorithm's strengths and limitations based on the use case. Limitations include that NHATS is not a "gold standard" for comparison of claims-based algorithms and we only analyzed NHATS respondents...

Two trees from the same species can vary in how they transport and manage water, improving specieswide drought resilience