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妊娠、子痫前期和母体衰老:从流行病学到功能基因组学。

Pregnancy, preeclampsia and maternal aging: From epidemiology to functional genomics.

机构信息

Department of Neurology, Division of Stroke and Cerebrovascular Disease, Columbia University Irving Medical Center, New York, NY, USA.

Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA.

出版信息

Ageing Res Rev. 2022 Jan;73:101535. doi: 10.1016/j.arr.2021.101535. Epub 2021 Dec 3.

Abstract

Women live longer than men but experience greater disability and a longer period of illness as they age. Despite clear sex differences in aging, the impact of pregnancy and its complications, such as preeclampsia, on aging is an underexplored area of geroscience. This review summarizes our current knowledge about the complex links between pregnancy and age-related diseases, including evidence from epidemiology, clinical research, and genetics. We discuss the relationship between normal and pathological pregnancy and maternal aging, using preeclampsia as a primary example. We review the results of human genetics studies of preeclampsia, including genome wide association studies (GWAS), and attempted to catalog genes involved in preeclampsia as a gateway to mechanisms underlying an increased risk of later life cardio- and neuro- vascular events. Lastly, we discuss challenges in interpreting the GWAS of preeclampsia and provide a functional genomics framework for future research needed to fully realize the promise of GWAS in identifying targets for geroprotective prevention and therapeutics against preeclampsia.

摘要

女性比男性长寿,但随着年龄的增长,她们会经历更大的残疾和更长的患病期。尽管衰老过程中存在明显的性别差异,但妊娠及其并发症(如子痫前期)对衰老的影响是老年医学中一个尚未充分探索的领域。本综述总结了我们目前关于妊娠与与年龄相关疾病之间复杂联系的知识,包括来自流行病学、临床研究和遗传学的证据。我们使用子痫前期作为主要示例,讨论了正常和病理性妊娠与母体衰老之间的关系。我们回顾了子痫前期的人类遗传学研究结果,包括全基因组关联研究(GWAS),并试图将与子痫前期相关的基因进行分类,作为深入了解晚年心血管和神经血管事件风险增加的机制的途径。最后,我们讨论了解释子痫前期 GWAS 面临的挑战,并为未来研究提供了一个功能基因组学框架,以充分实现 GWAS 在确定子痫前期的预防性和治疗性保护靶点方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7af/8827396/547267bf821a/nihms-1764243-f0001.jpg

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