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Alzheimer's disease (AD) is a neurodegenerative disorder characterised by progressive memory loss and cognitive decline. With the global population ageing, the prevalence of AD continues to rise, posing a significant public health challenge. Historically, AD research has centred on two hallmark pathological features: β-amyloid (Aβ) deposition and tau protein hyperphosphorylation. However, repeated failures of therapeutic strategies targeting these pathways in clinical trials have prompted a...

A 'gut-brain axis' is an intricate bidirectional connection between the gut and the central nervous system, serving as a key pathway for signal exchange. However, current in vitro models do not fully capture these dynamic interactions, limiting mechanistic insight and therapeutic testing. Here, we show a 3D human gut-brain-vascular microphysiological platform that integrates lumenized villus-like intestinal barrier, blood vascular-astrocyte interactions, and brain tissue to model...

Vestibular dysfunction becomes increasingly prevalent with aging and it is estimated that more than 80 % of people over 80 years old experience balance problems linked to vestibular dysfunction. Within the peripheral vestibular organs, sensory hair cells transform hair bundle motion into receptor potentials and information is next relayed to the brain by electrical activity in vestibular afferent nerves. There are three types of vestibular afferents: calyx-only afferents innervate one or more...

The nematode Caenorhabditis elegans is a favorable model for studying cell-surface protein interactomes, given its well-defined and stereotyped intercellular contacts. Here, we report an extracellular interactome dataset for C. elegans. Most of these interactions were unknown, despite recent datasets for flies and humans, as our collection contains a larger selection of protein families. We uncover interactions for all four major axon guidance pathways, including ectodomain interactions between...

Recent advances in biogerontology show that ageing is malleable, opening the possibility of delaying chronic disease and extending healthspan. Ethical debate has been dominated by consequentialist framings, balancing potential benefits against fears of overpopulation, inequality, or loss of meaning. We seek to further this discussion by grounding the case for longevity research not only in outcomes but also in respect for autonomy, self-ownership, and the intrinsic value of life itself. On this...

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by progressive memory loss and cognitive decline. With the global population ageing, the prevalence of AD continues to rise, posing a significant public health challenge. Historically, AD research has centred on two hallmark pathological features: β-amyloid (Aβ) deposition and tau protein hyperphosphorylation. However, repeated failures of therapeutic strategies targeting these pathways in clinical trials have prompted a...

Identification of ground contact timings (GCT) is critical for monitoring mobility in older adults. Laboratory methods are precise but limited to controlled environments, restricting their applicability in real-world settings. Treadmills allow extended measurements but fail to reflect the variability of overground walking. We evaluated the performance of deep learning models trained on treadmill data from young adults and their generalizability to treadmill and outdoor walking in older adults....

Visceral adipose tissue (VAT) inflammation is considered as an important contributor of aging, however, whether there is endogenous factor(s) in VAT that counteract this process remains obscure. Here we reported that interleukin (IL)-10 expressing B lineage (B-10) cells are greatly expanded in aged VAT in human and mouse. In aged VAT, B-10 cells are the primary source of IL-10. B cell-specific knockout of IL-10 exaggerated aging-related inflammation and insulin resistance (IR) and reduced...

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Aging is associated with increased susceptibility to metabolic stress and chronic liver disease, yet the interactions between age and metabolic stressors and the potential for ameliorating interventions remain incompletely understood. Here, we examined the hepatic response of young (7-month-old) and old (25-month-old) C57BL/6 male mice to a 9-week high-fat diet (HFD) and assessed whether rapamycin, a well-established pro-longevity intervention, could mitigate age-exacerbated effects. While both...

Early-life exposures could affect the risk of type 2 diabetes (T2D) in adulthood, but the mechanisms remain unclear. We included 319,951 (54.5% women) UK Biobank participants free of T2D at baseline and within the first year of follow-up to investigate whether early-life exposures contribute to T2D through biological aging estimated using the Klemera-Doubal (KDM) and PhenoAge methods. We first examined associations of exposures with biological age and T2D, respectively, using...

Dermal fibroblasts are pivotal in maintaining skin integrity through extracellular matrix (ECM) production, a process compromised during aging due to oxidative stress from excessive reactive oxygen species (ROS). Salvia miltiorrhiza Bunge (Danshen, DS), a medicinal plant rich in bioactive compound-rich dried roots, has demonstrated broad therapeutic potential. This study investigates the anti-aging properties of Danshen callus (DSC)-an undifferentiated cell mass derived from leaf tissue culture,...

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In recent years, the immune metabolism of central nervous system cells has gained increasing attention from researchers. Microglia (MG) are innate immune cells of the central nervous system. They can metabolize a wide range of energy substrates. The pathways and products generated through these processes play a critical role in the onset and progression of Alzheimer's disease (AD). This paper provides a comprehensive review of metabolic reprogramming in MG during AD. It focuses on the three...

Tumor-associated neutrophils (TANs) are abundant across cancers, yet their phenotypic diversity and functional states remain poorly defined. Here, we introduce a cell-type probability classifier that recovers low-transcript neutrophils from scRNAseq datasets, enabling pan-cancer analyses of TAN heterogeneity. Across >190 human and murine tumors, we identify a conserved differentiation trajectory that culminates in a terminal CCL3^(hi) state. This state exhibits pro-tumor transcriptional...

Stress granules (SGs) are membrane-less organelles formed through liquid-liquid phase separation of proteins and RNAs, serving as temporary repositories for biomacromolecules to protect cells under stress conditions. Impaired SG disassembly is closely implicated in neurodegenerative diseases and aging, yet the mechanisms regulating SG dynamics are incompletely investigated. The constituents of heterogenous SGs are complicated and broadly categorized as core and shell components. In contrary to...

As individuals age, cortical alterations in brain structure contribute to cognitive decline. However, the specific patterns of age-related changes and their impact on cognition remain poorly understood. This study assessed the effects of aging on individual gray matter similarity networks and compared them to anatomical and functional connectivity networks derived from diffusion-weighted imaging and resting-state fMRI, respectively. Our results showed that gray matter similarity networks...

Biopsychosocial frailty, a new construct combining modifiable physical, psychological, and social domains, was associated with increased risk of dementia, mild cognitive impairment, and their subtypes. The aim of the present study was to estimate the role of biopsychosocial frailty on the incident risk of cardio- and cerebrovascular disease, i.e., myocardial infarction, peripheral artery disease (PAD), and definite stroke. From the eight municipalities of the population-based Italian...

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