Ameliorative effects of NAD+ on D-galactose-induced senescence and susceptibility to Acinetobacter baumannii pneumonia via antioxidant and immune modulation.

Aging is a progressive process of multisystem physiological function decline driven by multiple factors, NAD+ is a potential compound for alleviating senescence. But the biological effects and mechanism of NAD+ against aging and aging-associated diseases are not fully elucidated. In this study, we first evaluated the protective effect of NAD+ on senescent cells, and then evaluated the blocking effect of aging and aging-associated pneumonia in vivo. The results showed that NAD+ could significantly improve the cell survival rate and oxidative stress, reduced the expression of aging markers and inflammatory factors. In animal experiments, NAD+ significantly improved the cognitive function of D-galactose induced aging mice by promoting the expression of BDNF, SYN and PSD-95. In addition, NAD+ can significantly enhance the activities of antioxidant enzymes, and reduce the release of proinflammatory cytokines. Quantitative real-time reverse transcription polymerase chain reaction results further showed that NAD+ could attenuate senescence induced cell cycle arrest by downregulating the expression of senescence-related genes such as p53, p21, and p16. Based on the aging mouse model induced by D-galactose, the acute pneumonia model was induced by Acinetobacter baumannii, a clinically relevant opportunistic pathogen. The results showed that the mice treated with NAD+ showed stronger resistance to pneumonia infection, the amount of bacterial colonization in the lungs decreased significantly and the weight loss was significantly improved. In terms of immune response, NAD+ improved the symptoms of pneumonia by enhancing humoral immunity and regulating cellular immunity. Therefore, as an effective agent for mitigating oxidative senescence, NAD+ holds potential as a dietary supplement to enhance health-span. SIGNIFICANCE STATEMENT: This study found that NAD+ can not only significantly improve the antioxidant capacity and cognitive function of aging mice, but also effectively enhance the immune defense of aging mice against bacterial infection, which provided experimental basis for its application in the prevention and treatment of aging and concurrent diseases.