Aggregator

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

Biology lies at the core of medicine, pharmacy, public health and longevity. However, in the physical world, biology is often too complex to manipulate and too expensive and risky to tamper with. In this Perspective, we put forward a vision of using AI to model and simulate biology and life. We present our vision on how to address this challenge through the construction of an AI-driven digital organism (AIDO)-a system of integrated multiscale foundation models-in a modular, connectable and...

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The pathogenesis of Alzheimer's disease (AD) involves multiple pathological processes, including β-amyloid (Aβ) deposition, aberrant tau modification, oxidative stress, and neuroinflammation. The molecular interaction mechanism among them remains to be further clarified. Peroxynitrite (ONOO⁻) is a potent oxidizing and nitrating reactive nitrogen species formed from the rapid reaction between nitric oxide and superoxide. It mediates protein nitration, lipid peroxidation, and mitochondrial damage,...

CONCLUSION: Temporal gait components were associated with age primarily through cognition-related pathways and may serve as candidate digital markers of cognitive impairment, although longitudinal validation is required. Interpretation is limited by the cross-sectional design and the restricted representation of individuals with moderate-to-severe dementia.

Intervertebral disc degeneration (IVDD) is a leading global cause of chronic pain and functional impairment. The senescence of endplate chondrocytes (EPCs) associated with the IVDD cascade, with mitochondrial homeostatic imbalance serving as the central pathological key mediator. EPCs inhabit a physiological niche defined by hypoxia, limited nutrients, and high mechanical loads, requiring precise metabolic regulation and mitochondrial quality control. This review integrates recent advances in...

Immunosenescence refers to the progressive decline in immune system functionality associated with aging, with thymic involution identified as a primary driver of this process. The thymus, the central organ for T cell development, begins to atrophy from puberty onward, resulting in a marked reduction in naive T cell output and a significant decrease in the diversity of T cell receptor (TCR) repertoires. This decline compromises the immune system's capacity to mount effective responses against...

Long-lived proteins provide a uniquely informative substrate for studying the molecular chemistry of human ageing, and the eye offers one of the most accessible and spatially resolved systems for examining this process. The lens remains the principal model: its central crystallins are synthesized during embryonic and early postnatal life and are retained throughout the lifespan, thereby preserving a cumulative record of irreversible chemical damage. We then extend this framework to other ocular...

Recently discovered genetic variants seem to protect against Alzheimer's disease, suggesting a path toward a cure. But are their powers believable?