Telomere Dynamics in Cardiovascular Aging: From Molecular Mechanisms to Precision Medicine

Telomere attrition stands as a fundamental hallmark of cardiovascular aging, driving cellular senescence and dysfunction across endothelial, cardiomyocyte, and vascular smooth muscle compartments. This review systematically examines: (1) molecular mechanisms linking telomere shortening to oxidative stress (NOX2/PRDX1 axis), epigenetic dysregulation (subtelomeric methylation, H3K9me3 loss), and mitochondrial dysfunction; (2) clinical evidence positioning leukocyte telomere length and telomere-associated proteins (eg, TRF2, POT1) as predictive biomarkers for coronary artery disease, heart failure, and hypertension; and (3) emerging therapeutic strategies ranging from telomerase activation (TA-65, GRN510) to senolytic cocktails (dasatinib + quercetin) and CRISPR (regularly interspersed short palindromic reportsclustered regularly interspaced short palindromic repeats)-based editing (6–29% efficiency in Chinese hamster ovary models). The review further addresses methodological challenges in telomere measurement (quantitative polymerase chain reaction (PCR) vs Flow-FISH standardization) and proposes an integrated risk assessment model combining leukocyte telomere length, oxidative markers (AGEs/sRAGE ratio), and epigenetic clocks. Translationally, we discuss tissue-specific delivery systems to mitigate oncogenic risks of telomerase therapies while emphasizing mitochondrial-targeted approaches for telomere stabilization. This synthesis bridges basic telomere science with clinical cardiology, offering a roadmap for personalized vascular rejuvenation strategies.