# A Bi-Adjuvant Senolytic Nanovaccine Modulating Dendritic Cell Senescence Ameliorates Aging-Related Metabolic Dysfunction

Article · Song Q, Du X, Dong W, Wang Y, Wang X, Yin Q

- Archive id: doi:10.1002/advs.78545
- Published: 2026-10-28
- Venue: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
- DOI: https://doi.org/10.1002/advs.78545
- PMID: 42949633
- Citations: 0
- Source URL: https://doi.org/10.1002/advs.78545
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Biology of Aging & Longevity](https://space-kitty.com/topics/aging-longevity)

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