Open AccessAn aged immune system drives senescence and ageing of solid organs
Author(s) -
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 Lü,
Tokio Sano,
Ryan D. O’Kelly,
Collin A. McGuckian,
Jonathan Kato,
Michael P. Bank,
Erin A. Wade,
Smitha P.S. Pillai,
Jenna Klug,
Warren Ladiges,
Christin E. Burd,
Sara E. Lewis,
Nicholas F. LaRusso,
Nam Vo,
Yinsheng Wang,
Eric E. Kelley,
Johnny Huard,
Ingunn M. Stromnes,
Paul D. Robbins,
Laura J. Niedernhofer
Publication year - 2021
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-021-03547-7
Subject(s) - immunosenescence , immune system , senescence , ageing , biology , immunology , transplantation , microbiology and biotechnology , medicine , genetics
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 5-7 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 8-10 . 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.