Author:
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 Jiangshan,Zhang Xiaojie,Li Jinbao,Zhao Yuwu,Wang Xiuzhe,Luo Yan,Zhou Ben,Zhang Haibing
Abstract
AbstractIn mammals, the most remarkable T cell variations with aging are the shrinking of naïve T cell pool and enlargement of memory T cell pool, which are partially caused by thymic involution. However, it remains an enigma whether these T-cell-related changes are consequences or causes of mammalian aging. In this study, we find that the T-cell specificRip1KO mice present similar age-related T cell changes and exhibit signs of accelerated aging, including inflammation, multiple age-related diseases and a shorter lifespan. Mechanistically, T cells lacking RIP1 displayed excessive apoptosis, leading to T cell compensatory proliferation, hyperactivation, increased inflammation, and ultimately premature death. Consistent with this, blocking apoptosis by co-deletion ofFaddinRip1deficient T cells significantly recovered the lymphopenia and imbalance between naïve and memory T cell, substantially restored ageing-related phenotypes, and prolonged life span in T-cell specificRip1KO mice. These results suggest that changes in T cells play a causal role in mammalian aging. Therefore, replenishing or blocking apoptosis of naïve T cells could offer new therapeutic approaches for aging and age-related diseases.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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1. T cell control of inflammaging;Seminars in Immunology;2023-11