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TLR2 regulation of NF-kappaB and NLRP3-driven pyroptosis in Alzheimer's disease

1 week 5 days ago
Although upregulation of toll-like receptor 2 (TLR2) excessively activates pro-inflammatory microglia through Aβ peptides, it remains unclear whether TLR2 regulates neuronal pyroptosis via the NF-κB/NLRP3 pathway in Alzheimer's disease (AD). We assessed TLR2 expression in peripheral blood from clinical samples and employed SH-SY5Y cells for initial screening. AD pathology was simulated by Aβ(1-42) stimulation, and pathway regulatory relationships were dissected through TLR2 knockdown, NF-κB...
Nijun Zhang

Oligodendrocytes at the crossroads: Central players and interactive partners in white matter aging

1 week 5 days ago
White matter degeneration in aging drives cognitive and motor decline. Oligodendrocytes (OLs) and their precursors are central to this process. Their intrinsic aging, marked by differentiation failure, metabolic and mitochondrial deficits, and transcriptional epigenetic dysregulation, causes myelin thinning and axonal support loss. Degeneration is amplified by dysfunctional crosstalk: microglia clear debris poorly and turn inflammatory; astrocytes disrupt lipid balance and secrete inflammatory...
Xinxin Zhang

Role of lysosomal morphology in aging and age-related diseases

1 week 5 days ago
Lysosomes are responsible for clearing cellular waste and facilitating material recycling, thus playing a crucial role in maintaining cellular homeostasis and even in resisting the development of various diseases. Lysosomes are highly dynamic organelles. While typically exhibiting a vesicular morphology, lysosomes can remodel into tubular structures under specific conditions; this morphological plasticity underpins their functional complexity. Aging triggers significant lysosomal morphological...
Huimin Liu

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

1 week 6 days 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 week 6 days 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 week 6 days 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...
Dan Zhong

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

1 week 6 days 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