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Carotid artery stenosis (CAS) often requires surgical intervention through carotid endarterectomy (CEA) to prevent stroke. Accurate cerebrovascular risk assessments are crucial in CEA, as poor collateral circulation can lead to insufficient interhemispheric blood flow compensation, resulting in ischemic complications. Therefore, understanding perioperative risk determinants is vital. This study aims to determine the impact of compromised circle of Willis (CoW) morphology on inter-hemispheric...

A long-lived species of zooplankton microcrustaceans, Daphnia magna, sometimes exhibits late-life rebound of reproduction, briefly reversing reproductive senescence. Such events are often interpreted as terminal investments in anticipation of imminent mortality. We demonstrate that such post-senescence reproductive events (PSREs) neither cause nor anticipate increased mortality. We analyze an RNAseq experiment comparing young, old reproductively senescent, and old PSRE Daphnia females. We first...

Clonal hematopoiesis of indeterminate potential (CHIP), marked by the accumulation of somatic mutations in hematopoietic stem cells, significantly elevates the risk of all-cause mortality, mainly due to cardiovascular events. Therefore, investigating this pathophysiological phenomenon is crucial for understanding cardiovascular aging and enhancing both health span and lifespan. In the present study, we examined samples of subjects enrolled within the angiographically controlled Verona Heart...

CONCLUSIONS: DAO was associated with increased odds for ADL disability among older adults from LMICs. Future longitudinal studies are warranted to assess temporal associations, and whether addressing or preventing DAO can impact on future occurrence of disability.

The study aimed to validate the protective effect of neuroglobin (Ngb) in a cell model of Parkinson's disease (PD) and explore its therapeutic potential. Lentivirus-Ngb (LvNgb) and siRNA-Ngb (siNgb) were used to achieve Ngb overexpression and knockdown, respectively, in a sporadic PD cell model. Apoptosis was evaluated by flow cytometry-based Annexin V/propidium iodide assays. Activation of the pro-apoptotic factor, Caspase-9, was detected by immunoblotting, and Complex I activities were...

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, with an unknown etiology and no specific treatment. Emerging single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have become instrumental in unravelling cellular heterogeneity and characterizing molecular signatures at single-cell resolution. Single-cell T cell receptor sequencing (scTCR-seq) and single-cell B cell receptor sequencing (scBCR-seq) technologies provide unprecedented...

Cerebrovascular abnormalities are critical indicators of stroke and neurodegenerative diseases like Alzheimer's disease (AD). Understanding the normal evolution of brain vessels is essential for detecting early deviations and enabling timely interventions. Here, for the first time, we proposed a pipeline exploring the joint evolution of cortical volumes (CVs) and arterial volumes (AVs) in a large cohort of 2841 individuals. Using advanced deep learning for vessel segmentation, we built normative...

Several major challenges, including an ageing population and declining workforce and the implementation of recent breakthrough therapies for Alzheimer disease, are prompting a necessary rethink of how people with neurodegenerative dementias are diagnosed and medically managed. Digital health technologies could play a pivotal part in this transformation, with new advances enabling the collection of millions of data points from a single individual. Possible applications include unobtrusive...

The Clinical Dementia Rating Sum of Boxes (CDR-SB) is a staging scale for Alzheimer's disease (AD)¹ and is commonly used as an outcome in clinical trials². It relies on information provided by the patient and an informant³. The CDR-SB should reflect only the patient's disease severity. However, we explored whether informant characteristics were associated with CDR-SB scores because that association might introduce bias in Alzheimer's disease research. We found that the CDR-SB was 0.20 higher...

Oxidative stress and cell senescence are both important drivers of ageing and age-associated disease and disability. In vitro, they are closely interconnected in a chicken-and-egg relationship: Not only is oxidative stress an important cause of cell senescence, but senescent cells are also sources of oxidative stress, obscuring cause-effect relationships during the ageing process. We hypothesize that cell senescence is a significant cause of tissue and systemic oxidative stress during ageing....

Nutrient-sensing pathways undergo deregulation in aged animals, exerting a pivotal role in regulating the cell cycle and subsequent stem cell division. Nevertheless, their precise functions in governing pluripotent stem cell differentiation remain largely elusive. Here, we uncovered a significant alteration in the cellular constituents of the intestinal epithelium in aged humans and mice. Employing Drosophila midgut and mouse organoid culture models, we made an observation regarding the altered...

Structural health monitoring ensures the safety and longevity of structures like buildings and bridges. As the volume and scale of structures and the impact of their failure continue to grow, there is a dire need for SHM techniques that are scalable, inexpensive, can operate passively without human intervention, and are customized for each mechanical structure without the need for complex baseline models. We present a novel "deploy-and-forget" approach for automated detection and localization of...

The actin cytoskeleton is a key determinant of cell structure and homeostasis. However, possible tissue-specific changes to actin dynamics during aging, notably brain aging, are not understood. Here, we show that there is an age-related increase in filamentous actin (F-actin) in Drosophila brains, which is counteracted by prolongevity interventions. Critically, decreasing F-actin levels in aging neurons prevents age-onset cognitive decline and extends organismal healthspan. Mechanistically, we...

Several major challenges, including an ageing population and declining workforce and the implementation of recent breakthrough therapies for Alzheimer disease, are prompting a necessary rethink of how people with neurodegenerative dementias are diagnosed and medically managed. Digital health technologies could play a pivotal part in this transformation, with new advances enabling the collection of millions of data points from a single individual. Possible applications include unobtrusive...

Protein fibril surfaces tend to generate toxic oligomers catalytically. To date, efforts to study the accelerated aggregation steps involved with Alzheimer's disease-linked amyloid-β (Aβ)-42 proteins on fibril surfaces have mainly relied on fluorophore-based analytics. Here, we visualize rare secondary nucleation events on the surface of Aβ-42 fibrils from embryonic to endpoint stages using liquid-based atomic force microscopy. Nanoscale imaging supported by atomic-scale molecular simulations...

The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell...

Cellular senescence is a stress-induced irreversible cell cycle arrest involved in tumor suppression and aging. Many stresses, such as telomere shortening and oncogene activation, induce senescence by damaging nuclear DNA. However, the mechanisms linking DNA damage to senescence remain unclear. Here, we show that DNA damage response (DDR) signaling to mitochondria triggers senescence. A genome-wide small interfering RNA screen implicated the outer mitochondrial transmembrane protein BNIP3 in...

Aging is an intricate process involving interactions among multiple factors, which is one of the main risks for chronic diseases, including Alzheimer's disease (AD). As a member of cysteine protease, cathepsin S (CTSS) has been implicated in inflammation across various diseases. Here, we investigated the role of neuronal CTSS in aging and AD started by examining CTSS expression in hippocampus neurons of aging mice and identified a significant increase, which was negatively correlated with...

Aging is an intricate process involving interactions among multiple factors, which is one of the main risks for chronic diseases, including Alzheimer's disease (AD). As a member of cysteine protease, cathepsin S (CTSS) has been implicated in inflammation across various diseases. Here, we investigated the role of neuronal CTSS in aging and AD started by examining CTSS expression in hippocampus neurons of aging mice and identified a significant increase, which was negatively correlated with...

Genome-scale metabolic models (GEMs) cover the entire list of metabolic genes in an organism and associated reactions, in a tissue/condition non-specific manner. RNA-seq provides crucial information to make the GEMs condition-specific. Integrative Metabolic Analysis Tool (iMAT) and Integrative Network Inference for Tissues (INIT) are the two most popular algorithms to create condition-specific GEMs from human transcriptome data. The normalization method of choice for raw RNA-seq count data...