{"id":"doi:10.1002/advs.78545","kind":"article","title":"A Bi-Adjuvant Senolytic Nanovaccine Modulating Dendritic Cell Senescence Ameliorates Aging-Related Metabolic Dysfunction","authors":["Song Q","Du X","Dong W","Wang Y","Wang X","Yin Q"],"author_count":6,"year":2026,"published":"2026-10-28","venue":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","cited_by":0,"doi":"10.1002/advs.78545","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/advs.78545","archive_url":"https://space-kitty.com/papers/doi:10.1002/advs.78545","updated":null,"pmid":"42949633","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Senolytic vaccines hold promise for eliminating senescent cells, but their efficacy is limited by poor seno-antigen immunogenicity and age-related dendritic cell (DC) dysfunction. Here, we engineered an active biomaterial-enabled bi-adjuvant senolytic nanovaccine (CK5-GC-NV) by co-assembling CpG oligodeoxynucleotide with a fusion protein of the seno-antigen Gpnmb and a cationic spider silk protein variant (CK5). Beyond antigen delivery, the CK5 scaffold acts as an intrinsic senomodulator associated with the downregulation of mitotic kinases Aurka/b and a concomitant decrease in senescence-associated PI3K/AKT phosphorylation in DCs. This intervention attenuates aged DC phenotypes, restores antigen cross-presentation, and synergizes with CpG to elicit potent cytotoxic T-lymphocyte responses against senescent targets. Across multiple aging mouse models, CK5-GC-NV immunization orchestrated targeted clearance of Gpnmb + senescent adipocytes, profoundly ameliorating metabolic dysfunction and extending lifespan. This multifunctional biomaterial platform integrates seno-antigen immunogenicity enhancement with the restoration of aged DC function, providing a promising proof-of-concept for antigen-directed gerotherapeutics.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"A Bi-Adjuvant Senolytic Nanovaccine Modulating Dendritic Cell Senescence Ameliorates Aging-Related Metabolic Dysfunction\" by Song Q, Du X, Dong W et al., https://doi.org/10.1002/advs.78545, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}