An aged immune system drives senescence and ageing of solid organs.
An aged immune system drives senescence and ageing of solid organs.
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衰老的免疫系统会导致实体器官的衰老。
DOI：
10.1038/s41586-021-03547-7
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发表时间：
2021-06
期刊：
影响因子：
64.8
通讯作者：
Niedernhofer LJ
中科院分区：
文献类型：
--
作者：
Yousefzadeh MJ;Flores RR;Zhu Y;Schmiechen ZC;Brooks RW;Trussoni CE;Cui Y;Angelini L;Lee KA;McGowan SJ;Burrack AL;Wang D;Dong Q;Lu A;Sano T;O'Kelly RD;McGuckian CA;Kato JI;Bank MP;Wade EA;Pillai SPS;Klug J;Ladiges WC;Burd CE;Lewis SE;LaRusso NF;Vo NV;Wang Y;Kelley EE;Huard J;Stromnes IM;Robbins PD;Niedernhofer LJ
免疫系统的老化，或免疫衰老，导致老年人的发病率和死亡率。为了确定免疫系统老化对机体衰老的贡献，这里我们选择性地删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，从而仅在免疫系统中衰老。我们发现Vav-iCre+/−；ERCC1ERCC1ERCC1−/fl小鼠在成年后是健康的，然后表现出过早的免疫衰老，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，类似于野生型小鼠在衰老过程中发生的变化。值得注意的是，非淋巴器官也表现出更多的衰老和损伤，这表明衰老的免疫细胞可以促进全身衰老。将Vav-ICre+/−、ERCC1−/fl或老龄野生型小鼠的脾细胞移植到幼龄小鼠体内可引起反式衰老，而年轻免疫细胞移植则可延缓衰老。雷帕霉素治疗Vav-iCre+/−；ERCC1−/fl小鼠减少了免疫细胞衰老的标志物，改善了免疫功能。这些数据表明，衰老的免疫系统在推动全身衰老方面具有因果作用，因此是延长健康老龄化的关键治疗目标。
Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence 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 mice. 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 function. 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.
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影响因子：
64.5
作者：
Burd CE;Sorrentino JA;Clark KS;Darr DB;Krishnamurthy J;Deal AM;Bardeesy N;Castrillon DH;Beach DH;Sharpless NE
通讯作者：
Sharpless NE
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
5.3
作者：
Nasto, Luigi A.;Wang, Dong;Robinson, Andria R.;Clauson, Cheryl L.;Ngo, Kevin;Dong, Qing;Roughley, Peter;Epperly, Michael;Huq, Saiful M.;Pola, Enrico;Sowa, Gwendolyn;Robbins, Paul D.;Kang, James;Niedernhofer, Laura J.;Vo, Nam V.
通讯作者：
Vo, Nam V.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ