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TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism

1 day 5 hours ago
Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in...
Astrid F Feiten

The m6A Epitranscriptome: A Regulatory Nexus Linking Cellular Senescence and Oncogenesis

1 day 5 hours ago
N⁶-methyladenosine (m⁶A) orchestrates RNA fate decisions through a dynamic interplay of writers, erasers, and readers, modulating splicing, stability, and translation. This review unveils how m⁶A fine-tunes senescence-associated pathways (p53/p21, p16-RB) with cancer-context-dependent duality-either as a tumor suppressor or promoter of progression/resistance. Leveraging single-cell and spatial omics, we dissect m⁶A's spatiotemporal heterogeneity in tumor-immune ecosystems. We consolidate...
Yao Xu

Exercise and the hallmarks of cardiovascular aging

1 day 5 hours ago
Cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis and myocardial infarction, remain the leading cause of morbidity and mortality worldwide. Aging is a predominant risk factor for CVD. Cardiovascular aging is characterized by progressive structural changes at the cellular level and functional decline within the cardiovascular system, ultimately contributing to the onset and progression of CVD. These changes include alterations in left ventricular (LV) systolic...
None Dan Zhong

The Association of Pain With Physical Performance Among Community-Dwelling Older Adults in the PRO-EVA Study

1 day 5 hours ago
CONCLUSIONS AND IMPLICATIONS: Chronic pain, especially its intensity, is independently associated with reduced physical performance in older adults. These findings reinforce the need for primary care services to prioritize the identification and management of chronic pain to help preserve mobility and functional capacity in aging populations.
Aline Dos Santos Mendes

Potential and challenges for sustainable progress in human longevity

1 day 5 hours ago
Decelerating gains in life expectancy (e(0)) in high-income countries have raised concerns about the future of human longevity. To enhance our understanding of these developments, we examine subnational (N = 450) mortality trends in Western Europe in the period 1992-2019. Between 1992 and 2005, gains in life expectancy were both substantial and widespread. Laggard regions experienced the fastest improvements, yielding rapid regional convergence. Between 2005 and 2019, however, gains in these...
Florian Bonnet

The interface of aging and salt in driving salt-sensitive hypertension: a comparative study in aged and young rats

1 day 5 hours ago
Hypertension prevalence is increasing in both aging and younger populations, with high salt intake being a key environmental driver. Whether young and aged individuals exhibit similar physiological and molecular responses to salt loading remains unclear. This study compared hemodynamic and renal redox adaptations to salt loading in young (8-week) and aged (50-week) Dahl salt-sensitive (DSS) rats. Both groups developed salt-sensitive hypertension, but blood pressure (BP) elevation was markedly...
Li Zeng

Optimizing cognitive functions in healthy older adults: a network meta-analysis of dual- and single-task interventions

1 day 5 hours ago
Physical and cognitive interventions, alone or combined, are recognized strategies to enhance cognitive function in healthy older adults, though their relative effectiveness remains debated. This study aimed to compare and classify the impact of such interventions on cognitive performance. Following PRISMA guidelines, randomized controlled trials (RCTs) were identified through searches of PubMed, Web of Science, and Scopus, with screening and data extraction procedures guided by the Cochrane...
Barbara Cazzolli

Peripheral cancer attenuates amyloid pathology in Alzheimer's disease via cystatin-c activation of TREM2

2 days 5 hours ago
Alzheimer's disease (AD) and cancer are among the most devastating diseases worldwide. Epidemiological data indicate that the incidence of AD significantly decreases in patients with a history of cancer. However, whether and how peripheral cancer may affect AD progression is yet to be studied. Here, we find that peripheral cancer inhibits amyloid pathology and rescues cognition via secretion of cystatin-c (Cyst-C), which binds amyloid oligomers and activates triggering receptor expressed on...
Xinyan Li

Establishing the relationship between brain cellular senescence and brain structure

2 days 5 hours ago
Cellular senescence and brain atrophy are both associated with brain aging, suggesting these processes may share underlying biological mechanisms. This study investigated these mechanisms by integrating structural neuroimaging with gene and protein expression data from prefrontal cortex tissue collected from individuals who underwent neurosurgery. Cell-type-specific gene expression signatures associated with neuroimaging features and cellular senescence were identified and replicated in several...
Anina N Lund

Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex

2 days 5 hours ago
We performed Visium spatial transcriptomics (ST) and single-nucleus RNA sequencing (snRNA-seq) on a cohort of nonpathological human tissues to uncover signatures of aging and senescence in the dorsolateral prefrontal cortex (dlPFC). In doing so, we identified gene expression changes characteristic of aged cortical layers. The cellular composition of the dlPFC also changed with age, with increased homeostatic astrocyte abundance and with decreased somatostatin (SST) inhibitory neurons. Nuclei...
Nicholas X Sloan

Cellular senescence in human liver under normal aging and cancer

2 days 5 hours ago
Cellular senescence, a stress-induced program causing stable cell-cycle arrest, is a hallmark of liver aging, fibrosis, and cancer. However, the cell-type-specific mechanisms, spatial organization, and cancer-associated alterations in the liver remain unclear. We profiled 43 normal human livers spanning ages and fibrosis stages using a single-cell multiome, Xenium spatial transcriptomics, and CODEX, complemented by fibrotic mouse models and 24 colorectal cancer liver metastases. We found CDKN1A+...
Alla Karpova

Evaluation of statistical differential analysis methods for identification of senescent cells using single-cell transcriptomics

2 days 5 hours ago
Differential gene expression (DGE) analysis is a crucial step in identifying senescent cells using single-cell RNA sequencing (scRNA-seq) data. However, few studies have evaluated the performance of DGE methods-particularly those implemented in the widely used Seurat package. In this study, we systematically assessed 10 DGE methods available in Seurat-Wilcox, Wilcox-limma, bimod, roc, t, negbinom, Poisson, LR, MAST, and DESeq2-using simulated and real scRNA-seq datasets. We evaluated each...
Dongmei Li

exBAClock: a comprehensive database of published clocks for age quantification and age-related diseases

2 days 5 hours ago
Biological age, as opposed to chronological age, quantifies the body's functional state and rate of aging. Despite the absence of a universal formula for its determination, panels of biomarkers that change consistently with age are used to construct predictive aging clocks. These models enable the identification of accelerated aging and are valuable as surrogate endpoints in clinical trials. The proliferation of published aging clocks has created a challenge: data is fragmented across numerous...
Anastasiya Kobelyatskaya