An aged immune system drives senescence and ageing of solid organs
By Matthew J. Yousefzadeh, Rafael R. Flores, Yi Zhu, Zoe C. Schmiechen, R. W. Brooks, Christy E. Trussoni, Yuxiang Cui, Luise A Angelini, Kyoo-a Lee, S. McGowan and 23 more. Nature, 2021
815 citations recorded by the source corpus.
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 intrans, 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. An aged, senescent immune system has a causal role in driving systemic ageing, and the targeting of senescent immune cells with senolytic drugs has the potential to suppress morbidities associated with old age.
Subfields: Epidemiology, Immunology, Physiology
View Paper: https://www.semanticscholar.org/paper/a4db61848b282a0e640f0f3ad0b098cca45310f4
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Citations in the corpus
- Immunosenescence: molecular mechanisms and diseases (2023, background): “Treg cells exhibit increased glucose and glycolytic metabolism and subsequently induce cellular senescence and an immunosuppressive microenvironment.(26) An increased proportion of Tregs is a significant obstacle to a successful immune response in age-related diseases.”
- Inflammation and aging: signaling pathways and intervention therapies (2023, background): “INFLAMMAGING AT THE ORGAN LEVEL As a result of the effects of cellular senescence, chronic inflammation, and immunosenescence, the pathological aging of organs increases the level of inflammation and makes repair difficult, ultimately leading to diseases.(10)”