NAD<sup>+</sup> supplementation prevents STING‐induced senescence in CD8<sup>+</sup> T cells by improving mitochondrial homeostasis
Bin Ye, Yingting Pei, Lujing Wang, Dehao Meng, Yu Zhang, Yu Zhang, Shuang Zou, Henian Li, Jinying Liu, Ziying Xie, Changhong Tian, Yuqi Jiang, Yu Qiao, Xu Gao, Yanfen Zhang, Yanfen Zhang, Ning Ma
Abstract
Abstract Understanding the connection between senescence phenotypes and mitochondrial dysfunction is crucial in aging and premature aging diseases. Loss of mitochondrial function leads to a decline in T cell function, which plays a significant role in this process. However, more research is required to determine if improving mitochondrial homeostasis alleviates senescence phenotypes. Our research has shown an association between NAD + and senescent T cells through the cGAS‐STING pathway, which can lead to an inflammatory phenotype. Further research is needed to fully understand the role of NAD + in T‐cell aging and how it can be utilized to improve mitochondrial homeostasis and alleviate senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence‐associated secretory phenotype (SASP) occur in senescent T cells and tumor‐bearing mice. Senescence is mediated by a stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD + levels with nicotinamide mononucleotide (NMN) prevents senescence and SASP by promoting mitophagy. NMN treatment also suppresses senescence and neuroinflammation and improves the survival cycle of mice. Encouraging mitophagy may be a useful strategy to prevent CD8 + T cells from senescence due to mitochondrial dysfunction. Additionally, supplementing with NMN to increase NAD + levels could enhance survival rates in mice while also reducing senescence and inflammation, and enhancing mitophagy as a potential therapeutic intervention.