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Microglial states underlying Alzheimer's disease (AD) have been well characterized in animal models and human samples, yet their regulation remains elusive. In this issue of Neuron, Zhu et al.¹ uncover Adgrg1, which governs a protective microglia phenotype through MYC activation.

Cellular deconvolution estimates cell-type fractions from bulk transcriptomic data, but current methods often overlook cell type-specific expression varying across samples, discrepancies between bulk and single-cell data, or lack guidance on reference data selection and integration. Therefore, we present BLEND, a hierarchical Bayesian method that leverages multiple single-cell reference datasets to perform cellular deconvolution. BLEND estimates cellular fractions accurately by learning the most...

CONCLUSIONS AND IMPLICATIONS: To prevent physical frailty in later life, acquiring regular eating habits may be important, especially in midlife.

To gain a more comprehensive understanding of the relationships among immunoscenescence and inflammaging, and subsequent epigenetic aging, we measured a panel of 43 immune cell phenotypes and 68 inflammatory proteins collected from blood samples provided by participants in the Framingham Heart Study Offspring Cohort at Exam 7 (1998-2001) and principal component-based DNA methylation (DNAm)-based biologic clocks measured at the subsequent exam (Exam 8 2005-2008), an average of 6 years later. A...

Intercellular nanotubular networks mediate material exchange, but their existence in neurons remains to be explored in detail. We identified long, thin dendritic filopodia forming direct dendrite-dendrite nanotubes (DNTs) in mammalian cortex. Super-resolution microscopy in dissociated neurons revealed DNTs' actin-rich composition and dynamics, enabling long-range calcium ion (Ca^(2+)) propagation. Imaging and machine learning-based analysis validated in situ DNTs as anatomically distinct from...

RNAs and RNA-binding proteins (RBPs) play crucial roles in stress granule (SG) dynamics, yet the specific interactions between SG-associated circular RNAs (circRNAs) and RBPs in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, we identified m6A-modified circG3BP1 as a potential prognostic biomarker in ESCC. Under cisplatin-induced stress, IGF2BPs facilitate the m6A-dependent translocation of circG3BP1 to SGs, where it functions as a scaffold to enhance TIAR-CAPRIN1...

Being a major contributor to cell senescence and aging, DNA damage activates macroautophagy/autophagy, but how this process is affected by aging-rewired metabolism in normal biological systems remains to be explored. Here in cultured human umbilical cord-derived mesenchymal stem cells (HsMSCs) and the mouse liver that accumulate DNA damage during aging, we found an elevation of DRAM1 (DNA damage regulated autophagy modulator 1) and DRAM1-mediated pro-senescent autophagy (DMPA). Confirming that...

Blood vessels exhibit a pronounced vulnerability to aging and are often at the forefront of systemic aging processes. Vascular endothelial cells, which line blood vessels and directly contact blood flow, are susceptible to damage and play a key role in vascular aging; however, the underlying mechanisms of their aging remain unclear. Here, we identify TRPM7 as a key molecule in vascular endothelial aging. Endothelial deletion of TRPM7 significantly accelerates premature vascular aging in mice....

We aimed to use multi-state models to assess joint impacts of lifestyle and genetic risk with phenotypic age acceleration on cardiometabolic multimorbidity (CMM) trajectory, and to further explore whether phenotypic age acceleration mediates association between lifestyle and each transitions. We conducted a prospective cohort study included 365,573 adults free of cardiometabolic diseases (CMDs) at baseline in UK Biobank. Multi-state model was used to calculate hazard ratios (HRs) and 95%...

Science, Volume 390, Issue 6768, October 2025.

Science, Volume 390, Issue 6768, October 2025.

Science, Volume 390, Issue 6768, October 2025.

Science, Volume 390, Issue 6768, October 2025.

Science, Volume 390, Issue 6768, October 2025.

Science, Volume 390, Issue 6768, October 2025.

Science, Volume 390, Issue 6768, October 2025.

Science, Volume 390, Issue 6768, October 2025.