小柯机器人

免疫系统衰老会导致实体器官衰老
2021-05-16 15:26

美国明尼苏达大学Laura J. Niedernhofer和Paul D. Robbins研究组合作取得最新进展。他们发现免疫系统衰老会导致实体器官衰老。该项研究成果发表在2021年5月12日出版的《自然》杂志上。

为了确定免疫系统衰老对机体衰老的贡献,他们有选择地敲除了小鼠造血细胞中编码关键DNA修复蛋白的Ercc1,以增加内源性DNA损伤的负担,从而仅使免疫系统衰老。他们显示Vav-iCre +/-; Ercc1- / fl小鼠成年后是健康的,然后表现出免疫衰老的过早发生,其特征是特定免疫细胞群的磨损和衰老以及免疫功能受损,类似于野生小鼠衰老过程中发生的变化。

值得注意的是,非淋巴器官还显示出衰老和损伤增加,这表明免疫细胞衰老可以促进全身衰老。从Vav-iCre +/-; Ercc1- / fl或衰老的野生型小鼠脾细胞向幼小小鼠的移植诱导其衰老,而幼小的免疫细胞的移植则减缓衰老。用雷帕霉素治疗Vav-iCre +/-; Ercc1- / fl小鼠可减少免疫细胞中的衰老标记并改善免疫功能。这些数据表明,免疫系统衰老在驱动系统性衰老中具有因果作用,因此代表了延长健康衰老的关键治疗目标。

据了解,免疫系统的衰老或免疫衰老会增加老年人的发病率和死亡率。

附:英文原文

Title: An aged immune system drives senescence and ageing of solid organs

Author: Matthew J. Yousefzadeh, Rafael R. Flores, Yi Zhu, Zoe C. Schmiechen, Robert W. Brooks, Christy E. Trussoni, Yuxiang Cui, Luise Angelini, Kyoo-A Lee, Sara J. McGowan, Adam L. Burrack, Dong Wang, Qing Dong, Aiping Lu, Tokio Sano, Ryan D. OKelly, Collin A. McGuckian, Jonathan I. Kato, Michael P. Bank, Erin A. Wade, Smitha P. S. Pillai, Jenna Klug, Warren C. Ladiges, Christin E. Burd, Sara E. Lewis, Nicholas F. LaRusso, Nam V. Vo, Yinsheng Wang, Eric E. Kelley, Johnny Huard, Ingunn M. Stromnes, Paul D. Robbins, Laura J. Niedernhofer

Issue&Volume: 2021-05-12

Abstract: Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly1,2. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein3,4, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence5,6,7 in the immune system only. We show that Vav-iCre+/;Ercc1/fl mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice8,9,10. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre+/;Ercc1/fl or aged wild-type mice into young mice induced senescence in trans, whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre+/;Ercc1/fl mice with rapamycin reduced markers of senescence in immune cells and improved immune function11,12. These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing.

DOI: 10.1038/s41586-021-03547-7

Source: https://www.nature.com/articles/s41586-021-03547-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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