Abstract
As aging progresses, the structures and functions of immune organs such as the thymus and spleen deteriorate, leading to impaired immune function and immune senescence. This study investigated the potential of umbilical cord mesenchymal stem cells (UC-MSCs) to mitigate D-galactose-induced immune senescence by enhancing the structural and functional integrity of aging immune organs and regulating the gut microbiota. The findings show that UC-MSCs treatment significantly delayed thymus and spleen atrophy and reduced the number of senescence-associated β-galactosidase (SA-β-gal) positive cells. At the molecular level, UC-MSCs treatment downregulated the expression of aging-related genes, including p16, p53, p21, and RB. It also boosted antioxidant enzyme activity, increasing the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), while decreasing serum malondialdehyde (MDA) levels by activating the Nrf2/HO-1 pathway. Additionally, UC-MSCs treatment restored the balance of the gut microbiota. These results demonstrate that UC-MSCs significantly improve the structural and functional integrity of immune organs and enhance the composition of the gut microbiome, offering a potential strategy for delaying immune senescence.