Scientists develop novel vaccine that targets aging cells
Aging is caused by the accumulation of poorly functional “senescent” cells, essentially old cells that do not proliferate. The elimination of senescent cells is thought to prevent aging and age-related disorders, including atherosclerosis. Scientists at Juntendo University Graduate School of Medicine, Japan, have developed a vaccine that targets a specific protein within senescent cells, thereby causing the cells’ elimination.
For the new study, the scientists first used a technique called transcriptome analysis to examine gene expression in senescent human cells, finding that glycoprotein nonmetastatic melanoma protein B (GPNMB) was expressed at high levels in these cells. This protein also had high expression levels in cells obtained from patients with atherosclerosis, a senescence-related disease involving plaque build-up and blockage in arteries.
The findings confirmed that GPNMB was a senescence-specific protein, i.e., a “seno-antigen.”
In a second experiment, in mice fed a high fat diet to speed up senescence, the removal of GPNMB was observed to cause fewer metabolic abnormalities and other molecular markers of aging, as well as less severe symptoms of atherosclerosis, compared to a group of control mice.
The scientists went on to develop a peptide-based vaccine that could target GPNMB and induce the immune system to destroy cells that expressed it. This was then tested in three groups: young mice on a high fat diet, middle-aged mice, and mice with an accelerated aging disease known as progeria.
All groups of mice showed distinct improvements: the high-fat-diet mice had better metabolic function once vaccinated; middle-aged mice that were vaccinated at 50 weeks of age remained more active and had faster movements by 70 weeks than control mice; while vaccinated progeroid mice had a significantly longer median lifespan, with the effect more pronounced in male mice.
[The results were compared alongside to three groups of unvaccinated mice.]
“Our study has demonstrated the possibility of a new anti-senescence strategy,” said Professor Tohru Minamino, a cellular senescence expert from Juntendo University. “We speculate that there are many more seno-antigens that are produced by other kinds of senescent cells. With more research we will be able to provide individualised anti-senescence therapy for patients depending on the prevalence of different types of senescent cells in their body.”
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