Ascorbic acid increases CD8+ T cells by binding Myh9 protein and enriching gut microbiota Akkermansia muciniphila, improves cognitive levels in middle-aged mice [scRNA-seq]

ABSTRACT: Immunosenescence hastens the process of systemic aging and impacts cognitive function, with antioxidants potentially ameliorating these consequences. This research systematically assessed the impact of ascorbic acid (vitamin C) on immunosenescence and cognitive function in middle-aged and elderly 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 binding protein Myh9. Additionally, 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. This study demonstrated that the administration of ascorbic acid can mitigate immunosenescence and, in conjunction with A. muciniphila, improve cognitive function in mice. These findings offer a mechanistic rationale for utilizing immunomodulatory interventions to enhance cognitive function, underscoring the significance of selecting the optimal route of administration for achieving the intended effects.

ORGANISM(S): Mus musculus

PROVIDER: GSE262964 | GEO | 2025/12/04

REPOSITORIES: GEO