Aminoacyl-tRNA synthetase-interacting multifunctional protein 3 (AIMP3), a tumor suppressor, mediates a progeroid phenotype in mice by downregulating lamin A. We investigated whether AIMP3 induces laminopathy and senescence of human aortic smooth muscle cells (HASMCs) and is associated with vascular aging in mice and humans in line with decreased lamin A expression. Cellular senescence was evaluated after transfecting HASMCs with AIMP3. Molecular analyses of genes encoding AIMP3, lamin A, chemokine (C-C motif) ligand 2 (CCL2), and C-C chemokine receptor type 2 (CCR2) and histological comparisons of aortas were performed with mice at various ages (7 weeks, 5 months, 12 months, 24 months, and 32 months), AIMP3-transgenic mice, and human femoral arteries of cadavers. AIMP3-transfected HASMCs exhibited increased AIMP3 and senescence marker p16 protein expression and decreased lamin A protein expression in accordance with their disrupted nuclear morphology in histological analyses. AIMP3-transgenic mice displayed increased AIMP3 protein expression and decreased lamin A protein expression in aortas together with typical aging pathologies. Similar changes were observed in wild-type aging (24-month-old) mice but not in wild-type young (7-week-old) mice. In humans, AIMP3 and lamin A protein expression was higher and lower, respectively, in femoral arteries of elderly individuals than in those of their younger counterparts. This study found that AIMP3 overexpression in vitro decreased lamin A expression and induced nuclear laminopathy and cellular senescence. Similar findings were made in the vasculature of aging mice and elderly humans.

氨酰-tRNA 合成酶相互作用多功能蛋白 3 (AIMP3) 是一种肿瘤抑制因子，通过下调 lamin A 介导小鼠早衰表型。小鼠和人类衰老与 lamin A 表达降低一致。用 AIMP3 转染 HASMC 后评估细胞衰老。对不同年龄（7 周、5 个月、12个月、24 个月和 32 个月），AIMP3-转基因小鼠和尸体的人股动脉。根据其在组织学分析中被破坏的核形态，AIMP3 转染的 HASMC 表现出增加的 AIMP3 和衰老标志物 p16 蛋白表达和降低的核纤层蛋白 A 蛋白表达。AIMP3-转基因小鼠在主动脉中显示增加的 AIMP3 蛋白表达和减少的 lamin A 蛋白表达以及典型的衰老病理。在野生型衰老（24 个月大）小鼠中观察到类似的变化，但在野生型年轻（7 周大）小鼠中没有观察到类似的变化。在人类中，AIMP3 和 lamin A 蛋白在老年人股动脉中的表达分别高于和低于年轻人。该研究发现体外 AIMP3 过表达降低了核纤层蛋白 A 的表达并诱导了核纤层蛋白病变和细胞衰老。在衰老小鼠和老年人的脉管系统中也有类似的发现。