An experimental vaccine helped to prolong the lives of mice and reverse some signs of age-related disease.
The experiment is a step on the way to a vaccine for humans, but could it really work?
The data was very strong and it was a good proof-of-principle, said Paul Robbins, a professor of biochemistry, molecular biology and biophysics and an associate director of the Institute on the Biology of Aging and Metabolism at the University of Minnesota. The approach would work in humans.
Robbins told Live Science that the big question was whether the vaccine would be safe in humans. To figure that out, the researchers would need to conduct more studies in animals and human patients.
According to the National Institute on Aging, senescent cells are cells that have stopped multiplying due to damage or stress, but don't die when they should. As we age, the immune system becomes less efficient at clearing these cells from the body.
The compounds released byescent cells cause inflammation and damage nearby healthy cells. Evidence shows that the build up of senescent cells contributes to a number of age-related diseases, including cancer, Alzheimer's and atherosclerosis, a disease where plaque builds up in the arteries.
Scientists have been working for the past decade to develop drugs that can clear senescent cells from the body. Some of the drugs have been shown to reduce inflammation, delay the start of age-related diseases and extend the life span of rodents. Robbins said that a few dozen of these drugs have entered clinical trials.
Robbins said that a vaccine could be used to target senescent cells, rather than drugs, and that people could be given the shot at a younger age.
A person taking senolytic drugs would need to take them repeatedly as senescent cells would reaccumulate after each course of treatment, whereas a person who was vaccine-free would need to look for senescent cells and destroy them on sight.
The senolytic vaccine was developed by the researchers because they chose a specific target for the immune system to aim at.
Different senescent cells look different than one another, because cells throughout the body can become senescent, according to senior author Dr. Tohru Minamino.
The team zeroed in on one cell type in the proof-of-concept study, senescent vascular endothelial cells, which line the insides of arteries, veins and capillaries. To find a good target for their vaccine, they analyzed the surfaces of the cells to see which proteins appeared in large quantities.
They picked one called "glycoprotein nonmetastatic melanoma protein B" (GPNMB), which seems to accumulate with age in some tissues and contribute to various diseases, according to a report in the journal Aging.
A report in the journal Steroids states that the same molecule appears in abundance on certain cancer cell types.
The team looked at tissue samples from patients with the disease and found that the cells of the vas deferens bore more GPNMB than those without the disease.
The team wanted to see if expunging GPNMB-heavy cells from the body would help with plaque build up.
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The team used a mouse model of atherosclerosis and eliminated GPNMB-positive cells from the rodents using genetic modification. The amount of plaque in the mice's arteries quickly decreased after they removed the cells. The team was able to make GPNMB the target of their vaccine.
The team created a vaccine that targets short segments of a longer sequence. The vaccine caused the immune system to build antibodies against parts of the GPNMB protein, which then tagged the attached cells for destruction.
In mice given the vaccine, GPNMB-positive cells, arterial plaques and inflammatory molecules were 888-609- 888-609- 888-609- 888-609- 888-609- They found that specific markers of senescence were reduced in the vaccine-vaccinated mice.
The team gave the vaccine to a little over a year old mice and then tested their agility at 1.5 years old. The team found that mice given a placebo shot were less active in their old age, but they still had more energy.
In a third experiment, the team found that mice given the vaccine lived slightly longer than mice given the placebo, suggesting that the shot may prolong life span.
Robbins said that the team didn't notice any side effects in their vaccine-vaccinated mice. One might expect some off-target effects since the GPNMB can be found on a variety of cells.
There will always be a concern that the vaccine might send the immune system after healthy cells without intending to, he said. The researchers will have to look out for the effects of the vaccine.
Minamino said that the team plans to develop additional vaccines that target different types of senescent cells, which may have different surface proteins that can be targeted by the immune system. The team will need to identify theUbiquitin and then make a vaccine to match it.
Robbins noted that they don't know what senescent cell subtype they should be targeting in anti-aging treatments and vaccines. We don't know if one senescent cell causes more trouble than another, but we do know that it may be.
There is a new National Institutes of Health grant called "The Cellular Senescence Network". He said that the goal of the field is to develop a senolytic vaccine or drug that can counter multiple aspects of aging in one go.
Nature Aging published new findings on December 10.
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The article was published by Live Science. The original article can be found here.
