NAD+ supplementation prevents STING‐induced senescence in CD8+ T cells by improving mitochondrial homeostasis

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 deter...

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Published in:Journal of cellular biochemistry 2024-03, Vol.125 (3), p.e30522-n/a
Main Authors: Ye, Bin, Pei, Yingting, Wang, Lujing, Meng, Dehao, Zhang, Yu, Zou, Shuang, Li, Henian, Liu, Jinying, Xie, Ziying, Tian, Changhong, Jiang, Yuqi, Qiao, Yu, Gao, Xu, Zhang, Yanfen, Ma, Ning
Format: Article
Language:English
Subjects:
Aging
CD8 antigen
cGAS‐STING
Homeostasis
Inflammation
Lymphocytes
Lymphocytes T
Mitochondria
Mitophagy
NAD
Nicotinamide
nicotinamide mononucleotide
Phenotypes
SASP
Senescence
Stimulators
Survival
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Summary: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.
ISSN:0730-2312
1097-4644
1097-4644
DOI:10.1002/jcb.30522