An aged immune system drives senescence and ageing of solid organs

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 Lu, Tokio Sano, Ryan D. O’Kelly, Collin A. McGuckian, Jonathan I. Kato, Michael P. Bank, Erin A. Wade, Smitha P. S. Pillai, Jenna Klug, Warren C. Ladiges, Christin E. Burd, Sara E. Lewis, Nicholas F. LaRusso, Nam V. Vo, Yinsheng Wang, Eric E. Kelley, Johnny Huard, Ingunn M. Stromnes, Paul D. Robbins () and Laura J. Niedernhofer ()
Additional contact information
Matthew J. Yousefzadeh: University of Minnesota
Rafael R. Flores: University of Minnesota
Yi Zhu: Robert and Arlene Kogod Center on Aging, Mayo Clinic
Zoe C. Schmiechen: University of Minnesota Medical School
Robert W. Brooks: The Scripps Research Institute
Christy E. Trussoni: Center for Cell Signaling in Gastroenterology, Mayo Clinic
Yuxiang Cui: University of California Riverside
Luise Angelini: University of Minnesota
Kyoo-A Lee: University of Minnesota
Sara J. McGowan: University of Minnesota
Adam L. Burrack: University of Minnesota Medical School
Dong Wang: University of Pittsburgh
Qing Dong: University of Pittsburgh
Aiping Lu: University of Texas Health Science Center at Houston
Tokio Sano: The Scripps Research Institute
Ryan D. O’Kelly: University of Minnesota
Collin A. McGuckian: University of Minnesota
Jonathan I. Kato: The Scripps Research Institute
Michael P. Bank: The Scripps Research Institute
Erin A. Wade: The Scripps Research Institute
Smitha P. S. Pillai: Fred Hutchinson Cancer Research Center
Jenna Klug: University of Washington
Warren C. Ladiges: University of Washington
Christin E. Burd: The Ohio State University
Sara E. Lewis: West Virginia University
Nicholas F. LaRusso: Center for Cell Signaling in Gastroenterology, Mayo Clinic
Nam V. Vo: University of Pittsburgh
Yinsheng Wang: University of California Riverside
Eric E. Kelley: West Virginia University
Johnny Huard: University of Texas Health Science Center at Houston
Ingunn M. Stromnes: University of Minnesota Medical School
Paul D. Robbins: University of Minnesota
Laura J. Niedernhofer: University of Minnesota

Nature, 2021, vol. 594, issue 7861, 100-105

Abstract: Abstract Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly1,2. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein3,4, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence5–7 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 mice8–10. 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 function11,12. 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (10)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03547-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:594:y:2021:i:7861:d:10.1038_s41586-021-03547-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03547-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().