An aged immune system drives senescence and ageing of solid organs
| Autor: | Ryan D. O’Kelly, Dong Wang, Tokio Sano, Warren C. Ladiges, Yinsheng Wang, Kyoo a. Lee, Johnny Huard, Sara J. McGowan, Ingunn M. Stromnes, Rafael R. Flores, Sara E. Lewis, Laura J. Niedernhofer, Robert W. Brooks, Aiping Lu, Zoe C. Schmiechen, Michael P. Bank, Nam Vo, Jenna Klug, Adam L. Burrack, Luise A. Angelini, Nicholas F. LaRusso, Qing Dong, Paul D. Robbins, Matthew J. Yousefzadeh, Christy E. Trussoni, Christin E. Burd, Smitha P. S. Pillai, Jonathan I. Kato, Yi Zhu, Yuxiang Cui, Erin A. Wade, Collin A. McGuckian, Eric E. Kelley |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Senescence Aging DNA Repair Immunosenescence DNA damage animal diseases Endogeny Biology Article Healthy Aging Mice 03 medical and health sciences 0302 clinical medicine Immune system Animals Homeostasis Rejuvenation Sirolimus Multidisciplinary biochemical phenomena metabolism and nutrition Endonucleases DNA-Binding Proteins Transplantation Haematopoiesis 030104 developmental biology Organ Specificity Ageing Immune System 030220 oncology & carcinogenesis Immunology bacteria Female Spleen DNA Damage |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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