Fungus drives spleen aging in mice, eased by astragaloside IV

In aged mice, exposure to the fungus Kazachstania pintolopesii accelerates splenic senescence, according to a study using sequencing and histopathological analyses. The fungal infection induced structural changes in the spleen, including white pulp lymphocyte rarefaction, mild interstitial fibrosis, and marked iron overload. It also remodeled immune subsets by driving naive T cells into effector and memory phenotypes, polarizing B cells toward a pro-senescent marginal zone profile, and triggering myeloid cell reprogramming with activated ferroptosis. These effects were driven by crosstalk between chronic inflammation and ferro-aging marked by iron accumulation and ACSL4-mediated lipid peroxidation. Administering the natural compound astragaloside IV attenuated these fungal-induced impairments. The intervention restored splenic immune function, regulated iron metabolism and redox homeostasis, suppressed ferroptosis signaling, and interrupted the feedback loop linking senescence to inflammation.