Nanovaccine loaded with seno-antigen target senescent cells to improve metabolic disorders of adipose tissue and cardiac dysfunction.

The buildup of senescent cells exacerbates metabolic disorders in adipose tissue and contributes to aging-related cardiac dysfunction. Targeted clearance of senescent cells can markedly ameliorate these aging-related diseases. Here, we developed a novel nanovaccine (GK-NaV) loaded with seno-antigen that is self-assembled from the fusion of cationic protein (K36) and seno-antigen peptide (Gpnmb). The GK-NaV could be highly engulfed by bone marrow-derived dendritic cells (BMDCs) and efficiently present antigens on the cellular surface, thereby promoting DCs maturation and activation of CD8⁺T cells in vitro. Following subcutaneous immunization, GK-NaV not only exhibited a noticeable antigen depot effect but also markedly activated specific cellular immune responses, enhancing the immunoreactivity and cytotoxic effects of CD8⁺T cells. Consequently, the targeted anti-aging immunity triggered by GK-NaV demonstrated the ability to selectively eliminate senescent adipocytes and cardiomyocytes in high-fat diet (HFD)-induced progeroid mice, leading to a significant improvement in age-related metabolic disorders in adipose tissue and cardiac dysfunction. Hence, our findings indicate that immunization with GK-NaV targeting seno-antigens may represent a promising strategy for novel senolytic therapies.