Cerebromicrovascular senescence in vascular cognitive impairment: does accelerated microvascular aging accompany atherosclerosis?

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Abstract Vascular cognitive impairment (VCI) is a leading cause of age-related decline, driven by cerebrovascular dysfunction and cerebral small vessel disease (CSVD). Emerging evidence suggests that cerebromicrovascular endothelial senescence plays an important role in the pathogenesis VCI promoting blood flow dysregulation, neurovascular uncoupling, blood–brain barrier (BBB) disruption, development microhemorrhages (CMHs). This review explores concept as continuum vascular aging, linking macrovascular atherosclerosis with microvascular dysfunction. It examines mechanisms which drives pathology highlights impact cardiovascular risk factors accelerating these processes. We examine preclinical clinical studies provide compelling atherosclerosis-induced exacerbates impairment. In particular, findings suggest targeting senescent cells through senolytic therapy can restore function improve outcomes experimental models atherosclerosis. Given growing recognition therapeutic target, further research warranted to explore novel interventions such senolytics, anti-inflammatory agents, metabolic modulators. The circulating biomarkers (e.g., senescence-associated secretory phenotype [SASP] components endothelial-derived extracellular vesicles) could enable early detection stratification individuals at high for VCI. Additionally, lifestyle modifications, including Mediterranean diet, hold promise delaying mitigating decline. conclusion, key mechanistic link between Addressing aging modifiable factor targeted offers promising strategy reducing burden preserving populations.

Language: Английский

Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

ABSTRACT Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double‐blind trial, 97 (78 men) undergoing bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 for two days pre‐surgery through hospital discharge. Primary outcomes reduced improved endothelial function ex vivo. Exploratory analyses included plasma proteomics single‐nuclei RNA sequencing of internal thoracic (ITA) samples. Quercetin treatment showed trend toward C‐reactive protein at discharge ( p = 0.073) differentially modulated circulating inflammatory expression between men women, pro‐inflammatory effect females. Endothelial acetylcholine‐induced relaxation significantly 0.049), effects 0.043) but not women 0.852). ITA transcriptomics revealed overexpression male cells, which reversed. female had minimal benefit increased fibroblasts. candidate target involves interactions receptor PLAUR ligands PLAU SERPINE1 . Post‐operative atrial fibrillation incidence was lower quercetin, representing 4% compared 18% group 0.033). conclusion, short‐term effectively CAD patients, improving functional outcomes. However, benefits observed patients. Trial Registration: https://clinicaltrials.gov , NCT04907253

Language: Английский