Excessive apoptosis of Rip1‐deficient T cells leads to premature aging.

Autor: Wang, Lingxia, Zhang, Xixi, Zhang, Haiwei, Lu, Kaili, Li, Ming, Li, Xiaoming, Ou, Yangjing, Zhao, Xiaoming, Wu, Xiaoxia, Wu, Xuanhui, Liu, Jianling, Xing, Mingyan, Liu, Han, Zhang, Yue, Tan, Yongchang, Li, Fang, Deng, Xiaoxue, Deng, Jiangshan, Zhang, Xiaojie, Li, Jinbao
Zdroj: EMBO Reports; 12/6/2023, Vol. 24 Issue 12, p1-15, 15p
Abstrakt: In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T‐cell changes and aging remains unclear. In this study, we find that T‐cell‐specific Rip1 KO mice show similar age‐related T cell changes and exhibit signs of accelerated aging‐like phenotypes, including inflammation, multiple age‐related diseases, and a shorter lifespan. Mechanistically, Rip1‐deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co‐deletion of Fadd in Rip1‐deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging‐like phenotypes, and prolongs life span in T‐cell‐specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age‐related diseases. Synopsis: T‐cell specific Rip1 KO mice show signs of accelerated aging‐like phenotypes, along with premature death. Blocking apoptosis by co‐deleting Fadd in Rip1tKO mice significantly rescues aging‐like phenotypes and prolongs shortened lifespan.Rip1tKO mice show similar age‐related T cell changes and exhibit signs of accelerated aging and a shorter lifespan.Rip1‐deficient T cells undergo excessive apoptosis, promoting chronic inflammation.Blocking necroptosis has little effect on the multimorbidity and premature aging seen in Rip1tKO mice.Blocking T cell apoptosis by co‐deleting Fadd rescues premature aging and multimorbidity in Rip1tKO mice. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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