CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Department of Neurology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
EMBO Rep. 2023 Dec 6;24(12):e57925. doi: 10.15252/embr.202357925. Epub 2023 Nov 15.
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.
在哺乳动物中，与衰老相关的最显著的 T 细胞变化是幼稚 T 细胞池的缩小和记忆 T 细胞池的扩大，这部分是由胸腺萎缩引起的。然而，T 细胞变化与衰老之间的关系的机制尚不清楚。在这项研究中，我们发现 T 细胞特异性的 Rip1 KO 小鼠表现出类似的与年龄相关的 T 细胞变化，并表现出加速衰老样表型的迹象，包括炎症、多种与年龄相关的疾病和寿命缩短。在机制上，Rip1 缺陷的 T 细胞经历过度凋亡，并促进慢性炎症。与此一致的是，通过共缺失 Fadd 在 Rip1 缺陷的 T 细胞中阻断细胞凋亡，可显著挽救淋巴细胞减少、幼稚 T 细胞和记忆 T 细胞之间的失衡以及衰老样表型，并延长 T 细胞特异性 Rip1 KO 小鼠的寿命。这些结果表明，T 细胞的减少和过度激活会对机体健康和寿命产生重大影响，强调了维持 T 细胞动态平衡对于健康衰老和预防或治疗与年龄相关的疾病的重要性。
