Researchers design a vaccine that kills certain cells responsible for aging

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Delaying or even stopping the aging process has been a topic of great interest for decades. Recently, a Japanese research team said they had developed a vaccine that kills so-called “zombie” cells that accumulate with age and damage neighboring cells. They cause diseases associated with aging, such as arterial stiffness and osteoporosis.

The objective of this new research is to achieve the use of an experimental vaccine as a treatment for arterial stiffness, diabetes and other diseases linked to aging. The results were published in the journal Nature Aging. Professor Toru Minamino from Juntendo University and his team observed that mice that received the vaccine showed a decrease in zombie cells, or senescent cells, and in areas affected by arterial stiffness.

As a reminder, the cells of the body can divide a certain number of times, then this ability disappears. They can then go into “senescence” before being eliminated. Far from being harmful throughout our lives, they have a protective function by sending molecular signals to other cells.

Thus, in young people, the balance between the formation and cleaning of senescent cells is optimal. But with age, the formation of these cells increases while their cleaning becomes less effective. As a result, they damage neighboring healthy cells by releasing chemicals that cause inflammation. Over time, they facilitate the aging process and pave the way for various pathologies: diabetes, osteoporosis, clogged arteries, age-related loss of muscle mass, etc.

A peptide vaccine against “zombie” cells

The Japanese team identified non-metastatic melanoma glycoprotein protein B (GPNMB) as a molecular target for senolytic therapy (which causes the destruction of senescent cells). In fact, the analysis revealed that GPNMB was a protein whose transmembrane domain was enriched in senescent cells in humans and mice.

The researchers then created a peptide vaccine based on an amino acid that makes up the protein. It allows the body to create antibodies that stick to senescent cells, which are removed by white blood cells that stick to the antibodies.

When they administered the vaccine to mice with blocked arteries, many accumulated senescent cells were killed and the areas affected by the disease were narrowed. According to the researchers, when the vaccine was administered to elderly mice elsewhere, their frailty progression was slower than that of unvaccinated mice.

Senolytic agents: side effects

Removal of senescent cells was already known to enhance normal and pathological changes associated with aging in mice. At the Mayo Clinic, James Kirkland and his team found two senolytic drugs to cleanse senescent cells: dasatinib, an anticancer drug, and quercetin, an anti-inflammatory flavonoid. This double treatment prolonged the life of the mice by a third (Nature Medicine, 2018). Metformin, used as a treatment for type 2 diabetes, is another example of a drug that can slow down aging.

However, most senolytic agents inhibit antiapoptotic pathways, increasing the possibility of off-target effects in normal tissue. The side effects of the new vaccine were minor, while its effectiveness lasted longer, the team said. Their results suggest that vaccination targeting senolytic antigens could be a potential strategy for new anti-aging therapies.

Nature Aging

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