Many of the all-too-familiar symptoms of aging can be attributed to a build-up of senescent cells, those which have stopped dividing. In a new study, researchers in Japan have identified a protein specific to these cells and developed a vaccine that can clear them away, with tests on mice reducing the effects of aging.
Cells cannot keep dividing forever – eventually they accumulate too much DNA damage through environmental stress, so the body shuts them down and flags them to be cleared out by the immune system. This seems to be an evolutionary defense mechanism against cells turning cancerous.
However, even immune cells aren’t immune from this process, and as they become senescent themselves the immune system gradually loses the ability to clear out senescent cells. As these inactive cells accumulate in the body, they contribute to symptoms of aging and the diseases that come with it.
In recent years scientists have been experimenting with a new class of drugs called senolytics that clear away these defunct cells, which have shown promise in slowing down the effects of aging and increasing lifespan and healthspan, the proportion of our lives we spend in good health.
For the new study, researchers in Japan set out to find a way to target senescent cells more directly while leaving healthy cells alone. By examining gene expression in senescent cells, the team first identified a protein called GPNMB, which is expressed in high levels by these defunct cells. This protein was also detected in high levels in patients with atherosclerosis, which is linked to senescence.
Next, the researchers tested what happened when GPNMB is removed. The team fed mice a high fat diet to speed up senescence, then genetically eliminated cells that expressed GPNMB. Sure enough, treated mice had fewer metabolic abnormalities and other molecular markers of aging, as well as less severe symptoms of atherosclerosis, than control mice.
While this experiment showed that targeting GPNMB can fight senescence and aging, genetic elimination of those cells isn’t something that can be easily done in humans. So the team developed a peptide-based vaccine that could target the protein 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.
Improvements were seen in all three groups. The high-fat-diet mice had better metabolic function than mice on the same diet that didn’t receive the vaccine. Middle-aged mice that were vaccinated at 50 weeks of age remained more active and had faster movements by 70 weeks than control mice. And vaccinated mice with progeria had a significantly longer median lifespan than unvaccinated animals, with the effect more pronounced in male mice.
Of course, there’s still plenty more work to be done before this exciting work could be translated into humans. The team says that GPNMB likely isn’t the only potential target either.
“Our study has demonstrated the possibility of a new anti-senescence strategy,” said Professor Tohru Minamino, corresponding author of the study. “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 individualized anti-senescence therapy for patients depending on the prevalence of different types of senescent cells in their body.”
The research was published in the journal Nature Aging.
Source: Juntendo University
