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Alzheimer's disease (AD) is an age-associated disorder characterized by cognitive decline, with dementia representing the final stage of a complex clinical-biological process rather than simply a more severe form of cognitive decline. Circular RNAs (circRNAs), novel non-coding RNAs, have emerged as key regulators of brain function and associated disorders. This study explores the role of circRNAs in AD by reviewing experimentally validated circRNAs in human and animal models. We identified 10...

With population aging, Alzheimer's disease (AD) is becoming increasingly prevalent, causing great health and economic burdens worldwide. Despite decades of research, there are still no effective disease-modifying treatments for AD, highlighting the urgent need for more in-depth understanding of the disease-causing mechanisms. The brain serotonin (5-HT) neurotransmission system undergoes structural and functional changes in aging and AD, which contributes to cognitive decline and comorbid mood...

A cell is governed by the interaction of myriads of macromolecules. Inferring such a network of interactions has remained an elusive milestone in cellular biology. Building on recent advances in large foundation models and their ability to learn without supervision, we present scPRINT, a large cell model for the inference of gene networks pre-trained on more than 50 million cells from the cellxgene database. Using innovative pretraining tasks and model architecture, scPRINT pushes large...

Little is known, how life-long hyperlipidaemia affects vascular ageing, before atherosclerosis. Here, we characterise effects of mild, life-long hyperlipidaemia on age-dependent endothelial dysfunction (ED) in humanised dyslipidaemia model of E3L.CETP mice. Vascular function was characterised using magnetic resonance imaging in vivo and wire myograph ex vivo. Plasma endothelial biomarkers and non-targeted proteomics in plasma and aorta were analysed. Early atherosclerosis lesions were...

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a^(R878H/+)), we discover that mutant HSPCs sustain elevated mitochondrial respiration which is associated with their resistance to aging-related changes in the bone marrow microenvironment. Mutant...

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Biobanks advance biomedical and clinical research by collecting and offering data and biological samples for numerous studies. However, the impact of these repositories varies greatly due to differences in their purpose, scope, governance, and data collected. Here, we computationally identified 2,663 biobanks and their textual mentions in 228,761 scientific articles, 16,210 grants, 15,469 patents, 1,769 clinical trials, and 9,468 public policy documents, helping characterize the academic...

The aggregation of α-synuclein (αSyn) is associated with Parkinson's disease and other related synucleinopathies. Considerable efforts have thus been directed at understanding this process. However, the recently discovered condensation pathway, which involves the formation of phase-separated liquid intermediate states, has added further complexity. In parallel, it has been reported that different αSyn splice isoforms may be implicated in aggregate formation in disease. In this study, we compare...

Chromosomal inversion polymorphisms can be common, but the causes of their persistence are often unclear. We propose a model for the maintenance of inversion polymorphism, which requires that some variants contribute antagonistically to two phenotypes, one of which has negative frequency-dependent fitness. These conditions yield a form of frequency-dependent disruptive selection, favoring two predominant haplotypes segregating alleles that favor opposing antagonistic phenotypes. An inversion...

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Environmental enrichment (EE) represents a robust experimental framework exploring the intricate interplay between genes and the environment in shaping brain development and function. EE is recognized as a non-invasive intervention, easily translatable to elderly human cohorts, and extrapolated from research on animal aging models. Age is the most important risk factor for ischemic stroke. Research indicates that EE, characterized by increased sensory, cognitive, and social stimulation, leads to...

H3 K27-altered spinal cord diffuse midline glioma (H3-SCDMG) poses therapeutic challenges. Analysis of 73 clinical samples revealed heightened proliferation in H3-SCDMG versus wild-type tumors, suggesting therapeutic vulnerabilities. Drug screening identified cytarabine (Ara-C) as highly effective in inhibiting proliferation in H3 K27M cell models, recently established patient-derived cells, and patient-derived xenograft models. Mechanistically, Ara-C can suppress tumor growth through DNA...

Aging is associated with dysregulated methionine metabolism and increased levels of enzymes in the tyrosine degradation pathway (TDP). To investigate the efficacy of targeting either methionine metabolism or the TDP for healthspan improvement in advanced age, we initiated dietary MetR or TDP inhibition in 18-month-old C57BL/6J mice. MetR significantly improved neuromuscular function, metabolic health, lung function, and frailty. In addition, we confirmed improved neuromuscular function from...

BackgroundAccurate classification of cognitive impairment in population studies is challenging.ObjectiveTo compare the performance of a diagnostic algorithm with a clinical consensus panel.SampleIn 2016, the Health and Retirement Study (HRS) implemented the Harmonized Cognitive Assessment Protocol Project (HRS-HCAP) to streamline cognitive assessments for select HRS participants.MethodsThe Manly-Jones HCAP diagnostic classification was used to classify cognitive status as normal, mild cognitive...

ObjectivesFew studies have investigated health outcomes associated with arthritis in low-middle-income countries. Our objective was to examine the association between arthritis and all-cause hospitalization and mortality among middle-aged and older adults in Mexico.MethodsOur sample included 12,106 participants aged >50 years from the 2012, 2015, and 2018 waves of the Mexican Health and Aging Study. Logistic regression was used for the associations between arthritis and hospitalization....