β‐1,3‐Glucan mediates innate immunity and anti‐aging effects in aged male <i>Nothobranchius guentheri</i> and protects against <i>Aeromonas hydrophila</i> infection

Abstract Immunosenescence, a hallmark of aging, increases susceptibility to microbial infections and chronic inflammation. Here, we explored age‐related innate immune alterations and the anti‐aging potential of β‐1,3‐glucan using the short‐lived annual fish Nothobranchius guentheri . A comparison of 6‐month‐old (adult) and 9‐month‐old (aged) male fish revealed that aging downregulated key innate immune genes ( bf , C3 , lysozyme , mbl1 , mbl2 , nk‐lysin , β‐defensin ) while upregulating pro‐inflammatory cytokines ( interferon‐γ , tnf‐α ) in the spleen, head kidney and liver. Aged fish were also much more susceptible to Aeromonas hydrophila infection, pointing to the occurrence of immunosenescence and inflammaging. Given this deteriorated immune status in aged fish, we next investigated whether β‐1,3‐glucan could alleviate age‐associated immune dysfunction and resist bacterial pathogen invasion. The data demonstrated that β‐1,3‐glucan pretreatment significantly improved the survival rate of aged fish (53.00% ± 3.33% vs. 33.00% ± 3.33% in controls) and reduced bacterial loads in immune tissues. Mechanistically, β‐1,3‐glucan enhanced infection‐induced expression of complement, mannan‐binding lectin pathway and antimicrobial peptide genes, while suppressing excessive pro‐inflammatory cytokine production in a time‐dependent (6–24 h post‐infection) manner. Collectively, our results demonstrate that β‐1,3‐glucan mitigates immunosenescence in aged N. guentheri by balancing antimicrobial defence and inflammatory responses, highlighting its potential as a nutritional intervention for enhancing innate immunity and combating age‐related infection susceptibility.