Enhancing the Anti-Aging Capacity of hUC-MSCs via NMN Co-Treatment in D-Galactose-Induced Mice and Cellular Senescence Models.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have emerged as a promising therapeutic option for anti-aging therapy. However, the aging 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-aging 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 aging 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-aging properties. Taken together, our study provides a promising combinatorial approach that sustains stem cell function and amplifies anti-aging efficacy.