Using 3 independent mouse models (mice with iWAT removal, mice with iWAT-specific CYP26C1 overexpression, and naturally aging mice), we demonstrate that sWAT dysfunctions, including diminished RA secretion and sWAT loss, contribute to aging-like intestinal dysfunctions, including reduced IgA production, systemic endotoxemia, microbiota dysbiosis, and pathogen infection. The gene discussed is CD79A; the disease is infection.