BACKGROUND:Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia.METHODS:We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average.RESULTS:Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho (P=0.018); increased leptin (P=0.016) and leptin/adiponectin ratio (P=0.027), and increased extracellular vesicles positive for tissue factor (P=0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment (P=0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women (P=0.003).CONCLUSIONS:Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia.

中文翻译：

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有先兆子痫病史的女性表现出加速衰老和不利的衰老标志物特征


背景：衰老是一种细胞衰老机制，其特征是不可逆的增殖停滞和促炎性分泌表型，已在患有先兆子痫的女性中得到记录。由于细胞衰老可以持续和进展，我们推测它与有先兆子痫病史的女性加速衰老表型和合并症的积累有关。 方法：我们纳入了一组有先兆子痫病史的女性 (n = 40)并与一组血压正常的妊娠女性（n=40）进行奇偶匹配。先前患有重大心血管事件、神经系统或自身免疫性疾病的女性被排除在外。我们收集了尿液和血液样本，以研究衰老标志物、入组时的多发病数据，并前瞻性地跟踪她们平均 6 年的事件。 结果：有先兆子痫病史的女性与其他女性相比，表现出不利的衰老特征。涉及女性，包括尿 α-Klotho 减少（ P =0.018）；瘦素（ P =0.016）和瘦素/脂联素比值（ P =0.027）增加，组织因子阳性细胞外囊泡增加（ P =0.025）。同样，有先兆子痫病史的女性在入组时的合并症发生率也较高 ( P = 0.003)，并且与参考女性相比，发生重大心血管事件的风险高出 4 倍 ( P = 0.003)。结论：我们的数据表明先兆子痫病史与衰老标志物差异和晚年多种疾病累积所表明的加速衰老有关。 针对细胞衰老可能为有先兆子痫病史的女性的不良健康结果的诊断和治疗提供新颖的、基于机制的方法。