Ascorbic acid improves cognitive levels in middle-aged mice and increases CD8 + T cells by binding Myh9 protein and enriches gut microbiota Akkermansia muciniphila

Abstract Background: Immunosenescence accelerates systemic aging and influences cognitive function, with antioxidants potentially mitigating these effects. The significance of ascorbic acid (vitamin C) as a crucial antioxidant in anti-aging and cognition, as well as the potential impact of the gut microbiome on this process, has yet to be investigated. Results: In this study, we systematically assessed the impact of ascorbic acid on immunosenescence and cognitive function in middle-aged and aged mice. The findings demonstrated a notable rise in peripheral blood lymphocytes, a decline in myeloid immune cells, and enhanced cognitive performance. In vitro studies indicated that ascorbic acid facilitated the differentiation of mouse hematopoietic stem cells (HSCs) and spleen monocytes into CD8+ T cells, with its efficacy primarily mediated by its interaction with the protein Myh9 protein. A positive correlation was observed between CD8+ T cells and cognitive function. Furthermore, a distinction exists between the efficacy of oral and intravenous administration of ascorbic acid in enhancing cognitive function, potentially attributable to the modulation of the gut microbiome Akkermansia muciniphila. Intravenous delivery notably enhances A. muciniphila abundance and significantly enhances cognitive performance in middle-aged and elderly mice, whereas oral ascorbic acid supplementation increases CD8+ T cell count and cognitive function in this demographic only when co-administered with A. muciniphila. Conclusion: This study demonstrated that the administration of ascorbic acid can mitigate immunosenescence and, in conjunction with A. muciniphila, improves cognitive function in mice. These findings offer a mechanistic rationale for utilizing nutritional interventions to mitigate immunosenescence and enhance cognitive function, and underscores the importance of selecting the optimal route of administration for achieving the intended effects.