Enhancing the anti-ageing capacity of hUC-MSCs via NMN co-treatment in D-galactose-induced ageing mice and cellular senescence models

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have emerged as a promising therapeutic option for anti-ageing therapy. However, the ageing microenvironment can induce oxidative stress and senescence in transplanted hUC-MSCs, thereby impairing their capacity to delay immunosenescence. Combining MSC-based therapy with antioxidants may enhance therapeutic efficacy. This study explored whether hUC-MSCs could exert enhanced anti-immunosenescence effects when administered in combination with nicotinamide mononucleotide (NMN). Compared with either treatment alone, the combined administration exerted enhanced anti-ageing efficacy, as evidenced by marked alleviation of thymic and splenic atrophy, attenuation of body weight loss, and significant improvement in motor and cognitive functions in D-galactose-induced ageing mice. In vitro results indicated that combined treatment with hUC-MSCs and NMN alleviated cellular senescence in lymphocytes while simultaneously reducing oxidative stress and senescence in hUC-MSCs. Mechanistically, activation of the Nrf2/HO-1 pathway by NMN mitigated hUC-MSC senescence under stress conditions, thereby preserving their anti-ageing properties. Taken together, our study provides a promising combinatorial approach that sustains stem cell function and amplifies anti-ageing efficacy.