衰老是生物体结构和生理功能的一系列退行性变化。 JPX——一种我们新发现的与年龄相关的非编码RNA——是否与动脉粥样硬化有关仍不清楚。我们的研究旨在调查 JPX 的作用，并为针对动脉粥样硬化的潜在疗法提供见解。我们分析了包括半月板组织、白血病细胞和外周血单核细胞在内的多种组织的临床数据，以鉴定衰老血管平滑肌细胞中与年龄相关的非编码 RNA。 VSMC）。通过RNA靶标的捕获杂交分析和染色质免疫沉淀研究JPX的分子机制。使用 IGVTools 和实时定量聚合酶链反应评估年龄相关疾病模型表型调节过程中的 JPX 表达。在平滑肌特异性JPX敲除小鼠中建立动脉粥样硬化模型后，评估了JPX的治疗潜力。Ras诱导的衰老VSMC和动脉粥样硬化动脉中JPX表达上调。 JPX 敲低显着降低了衰老 VSMC 中衰老相关分泌表型 (SASP) 基因的升高。细胞质 DNA 通过 VDAC1（电压依赖性阴离子通道 1）低聚物形成的线粒体通透性转换孔从线粒体泄漏，激活 STING（干扰素基因刺激剂）途径。 JPX可以作为SASP基因的增强子，并通过与染色质重塑复合物中磷酸化的P65和BRD4（含溴结构域蛋白4）相互作用，充当支架分子，通过表观遗传调控促进SASP基因的转录。 ApoeKO小鼠平滑肌敲除JPX，与对照组相比，斑块面积减少，SASP基因表达减少，衰老减少。JPX作为增强子RNA，可以整合P65和BRD4形成染色质重塑复合物，激活SASP基因转录并促进细胞衰老。这些发现表明 JPX 是治疗年龄相关动脉粥样硬化的潜在治疗靶点。

Senescence is a series of degenerative changes in the structure and physiological function of an organism. Whether JPX-a newly identified age-related noncoding RNA by us-is associated with atherosclerosis is still unknown. Our study was to investigate the role of JPX and provide insights into potential therapies targeting atherosclerosis.We analyzed clinical data from multiple tissues including meniscus tissue, leukemia cells, and peripheral blood monocytes to identify age-related noncoding RNAs in senescent vascular smooth muscle cells (VSMCs). The molecular mechanism of JPX was investigated by capture hybridization analysis of RNA targets and chromatin immunoprecipitation. IGVTools and real-time quantitative polymerase chain reaction were used to evaluate the JPX expression during phenotype regulation in age-related disease models. The therapeutic potential of JPX was evaluated after establishing an atherosclerosis model in smooth muscle-specific JPX knockout mice.JPX expression was upregulated in Ras-induced senescent VSMCs and atherosclerotic arteries. JPX knockdown substantially reduced the elevation of senescence-associated secretory phenotype (SASP) genes in senescent VSMCs. Cytoplasmic DNA leaked from mitochondria via mitochondrial permeability transition pore formed by VDAC1 (voltage-dependent anion channel 1) oligomer activates the STING (stimulator of interferon gene) pathway. JPX could act as an enhancer for the SASP genes and functions as a scaffold molecule through interacting with phosphorylated P65 and BRD4 (bromodomain-containing protein 4) in chromatin remodeling complex, promoting the transcription of SASP genes via epigenetic regulation. Smooth muscle knockout of JPX in ApoeKO mice resulted in a decrease in plaque area, a reduction in SASP gene expression, and a decrease in senescence compared with controls.As an enhancer RNA, JPX can integrate P65 and BRD4 to form a chromatin remodeling complex, activating SASP gene transcription and promoting cellular senescence. These findings suggest that JPX is a potential therapeutic target for the treatment of age-related atherosclerosis.