An aged immune system drives senescence and ageing of solid organs

May 13, 2021Nature

An aging immune system may cause aging and cell breakdown in solid organs

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Abstract

Selective deletion of Ercc1 in mouse immune cells led to premature onset of immunosenescence.

Vav-iCre;Ercc1 mice exhibited early signs of immune system aging, including loss and aging of specific immune cell populations.
Impaired immune function in these mice resembled that of older wild-type mice.
Increased senescence and damage were also observed in non-lymphoid organs, indicating a potential role of aged immune cells in systemic aging.
Transplanting splenocytes from aged mice into young mice caused senescence in the recipient's immune cells, while young splenocytes reduced signs of aging.
Treatment with rapamycin decreased markers of senescence in immune cells and improved immune function in Vav-iCre;Ercc1 mice.

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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 senescencein the immune system only. We show that Vav-iCre;Ercc1mice 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;Ercc1or 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;Ercc1mice 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. 1,2 3,4 5-7 +/--/fl8-10 +/--/fl +/--/fl11,12

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An aged immune system drives senescence and ageing of solid organs

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