A vaccine targeting senescent fat cells given to female mice at 75 weeks of age yielded a median lifespan of 113 weeks, compared with 101 weeks in mice given saline
A vaccine targeting senescent fat cells given to female mice at 75 weeks of age yielded a median lifespan of 113 weeks, compared with 101 weeks in mice given saline
On October 28, Advanced Science published a study by a group at the First Hospital of Jilin University on a vaccine that extended the lifespan of female mice in three models of aging.
The vaccine is designed to work as follows: dendritic cells take up the injected target protein and present it to killer T cells (identified by the marker CD8⁺), which then destroy cells carrying that protein. The target was Gpnmb, a protein found in senescent cells and described as a senescence-associated antigen. In 2021, a group at Juntendo University in Tokyo showed that genetically eliminating cells carrying this protein reduced adipose tissue senescence in mice on a high-fat diet, while vaccination against it extended the lifespan of male mice with premature aging. In 2024, the same Jilin group reported that a protein vaccine had little effect in old mice and that their dendritic cells took up antigen less efficiently. A vaccine consisting of dendritic cells loaded with antigen outside the body was effective, however. In 2025, researchers at the same hospital vaccinated eight-week-old mice with a nanovaccine based on the carrier protein K36.
The new vaccine is a nanoparticle composed of CpG DNA fragments and the carrier protein CK5 (a spider silk variant) with Gpnmb attached. CK5 helps the antigen enter dendritic cells, while immune cells recognize CpG as a sign of bacteria and initiate an immune response. In cultured dendritic cells treated with CK5 alone, levels of the cell division enzymes Aurka and Aurkb fell, and PI3K/AKT signaling activity decreased; the K36 carrier had little effect on this pathway. CK5 also reduced senescence markers in cells in which senescence had been induced by the sugar D-galactose. Citing earlier studies, the authors write:
“Senescent dendritic cells have intrinsically overactive PI3K/AKT signaling, which disables their ability to initiate a CD8⁺ T-cell response against senescence-associated antigens.”
In the main experiment, female mice on a standard diet, with ten mice per group, were vaccinated at 75 weeks of age. Vaccinated mice had a median lifespan of 113 weeks, compared with 101 weeks in mice given saline. Three comparisons tested the role of dendritic cells. A vaccine using the alternative carrier K36 yielded a median lifespan of 103 weeks. Adding danusertib, a drug targeting the same enzymes, Aurka and Aurkb, to the K36 vaccine increased the median lifespan to 111 weeks. In mice with D-galactose-induced accelerated aging, the researchers injected dendritic cells from young mice that had been loaded with the K36 vaccine in culture. Median lifespan increased to 109 weeks, compared with 103,5 weeks with unloaded cells, while the CK5 vaccine yielded a median lifespan of 112 weeks. In mice on a high-fat diet, vaccination at 60 weeks yielded a median lifespan of 91 weeks, compared with 79–83 weeks in the control groups.
In the main experiment, mice given the CK5 vaccine had 2,7-fold lower activity of β-galactosidase, a marker of senescent cells, in the fat surrounding their internal organs than control mice. They also had better glucose tolerance and greater insulin sensitivity, with the same body weight and food intake as controls. In culture, T cells from vaccinated mice on a high-fat diet killed senescent immature fat cells with high Gpnmb levels more effectively than T cells from control mice, and the proportion of fat cells carrying Gpnmb was approximately 3,5-fold lower.
Ten weeks after vaccination, the proportion of memory T cells in mice on a high-fat diet was 3,2-fold higher than in controls. Dendritic cells are short-lived, and the authors propose that memory T cells sustain the effect of a single vaccination by providing “continuous immune surveillance” and eliminating senescent cells as they appear.