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 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.

Liposome-embedded SOD attenuated DSS-induced ulcerative colitis in mice by ameliorating oxidative stress and intestinal barrier dysfunction.

Oxidative stress is generally considered inseparable from the development and exacerbation of ulcerative colitis (UC). Therefore, reducing oxidative stress has become a possible way to alleviate UC. In this study, the therapeutic effects of different doses of liposome-embedded superoxide dismutase (L-SOD) on mice with DSS-induced UC were systematically investigated. The results showed that L-SOD significantly attenuated the signs of colitis in mice, including colonic shortening, diarrhoea, bloody stools, and histopathological changes. L-SOD ameliorated DSS-induced oxidative damage, increased SOD, catalase (CAT), and glutathione (GSH) activities, and decreased malondialdehyde (MDA) levels. In addition, L-SOD ameliorated the inflammatory response by inhibiting the expression of myeloperoxidase (MPO) and pro-inflammatory cytokines and protected barrier function by promoting the expression of the tight junction proteins occludin and ZO-1 in the colon. Importantly, the results demonstrated a bell-shaped distribution of therapeutic effects relative to the administered dose, with an optimal dose of 150 000 U kg-1. These results indicate that L-SOD has great potential as an ingredient in functional foods for the prevention and mitigation of UC.