Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly^1,2. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein^3,4, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence^5,6,7 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 mice^8,9,10. 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 function^11,12. 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.

免疫系统老化或免疫衰老会导致老年人^1,2的发病率和死亡率。为了确定免疫系统衰老对生物体衰老的贡献，我们在小鼠造血细胞中选择性地删除了编码关键 DNA 修复蛋白^3,4的Ercc1 ，以增加内源性 DNA 损伤的负担，从而增加小鼠造血细胞中的衰老^5,6,7只有免疫系统。我们证明了Vav-iCre ^+/- ;Ercc1 ^-/fl小鼠健康到成年，然后表现出过早发生的免疫衰老，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^8,9,10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衰老和损伤增加，这表明衰老的免疫细胞可以促进全身衰老。将来自Vav-iCre ^+/- ;Ercc1 ^-/fl或老年野生型小鼠的脾细胞移植到年轻小鼠体内会诱导反式衰老， 而年轻免疫细胞的移植会减弱衰老。Vav-iCre ^+/- ;Ercc1 ^{-/fl 的}处理使用雷帕霉素的小鼠减少了免疫细胞中的衰老标志物并改善了免疫功能^11,12。这些数据表明，衰老的、衰老的免疫系统在驱动系统性衰老方面具有因果作用，因此代表了延长健康衰老的关键治疗靶点。