Vaccines don't just prevent disease: they could also combat aging.

What if the very cells that drive aging could be the key to slowing it down... and even putting cancer on the back foot? This is the new challenge of a new field of research that proposes using senescent cells —those that have stopped dividing and accumulate with age—as a basis for developing vaccines. The goal is to activate the immune system to combat chronic diseases.
Aging is one of the main risk factors for diseases such as Alzheimer's, type 2 diabetes, hypertension, atherosclerosis, osteoarthritis, fibrosis , and several types of cancer. As we live longer, the need for strategies to prevent or treat these conditions also increases.
In this context, vaccination—until now used primarily to prevent infections—is undoubtedly emerging as an innovative tool.
Throughout life, cells divide many times, a process that helps repair tissues and keep the body functioning. But over time, some cells stop dividing permanently: this is known as cellular senescence.
Senescent cells neither die nor are eliminated. They remain in the body in a kind of indefinite "pause." Initially, this has a positive effect: by stopping dividing, they prevent dangerous mutations from developing into cancer. But over the years, they accumulate in tissues, releasing substances that cause inflammation, alter the cellular environment, and impair body function.
The accumulation of these cells is one of the causes of aging. It is linked to organ deterioration and diseases such as osteoporosis, fibrosis, type 2 diabetes, and several types of cancer, as well as a weakened immune system.
In short, they are like "timekeepers" in our bodies: initially they protect us, but over the years they become a burden that accelerates aging and its effects.
Until now, so-called senolytic treatments—which specifically eliminate senescent cells—have been drug-based. These drugs block certain cellular defense mechanisms, but they can also affect healthy cells, raising concerns about their safety.
In a 2021 study , researchers discovered a more precise strategy: instead of using drugs, they developed a vaccine that trains the immune system to recognize and eliminate senescent cells. The secret lies in a protein called GPNMB, present on the surface of these aging cells. By acting as an "aging marker," it allows the immune system to detect and destroy them.
The results in mice were remarkable. By eliminating cells expressing GPNMB, the animals showed reduced inflammation in adipose tissue. An overall improvement in their metabolism and less plaque buildup in their arteries were also observed. Furthermore, in mice with accelerated aging, the vaccine not only improved their health but also extended their lifespan.
In another study , scientists tested a vaccine designed to eliminate senescent T cells or lymphocytes in mice with obesity induced by a high-fat diet. This time, it's based on the protein CD153, which acts as a specific marker for these aging immune system cells.
When the mice were vaccinated, their immune systems began producing antibodies against CD153. These antibodies remained active for several months and significantly reduced the number of senescent T cells in fatty tissue, a reduction associated with significant metabolic improvements: improved glucose tolerance and reduced insulin resistance.
Finally, another group of scientists recently used the BCG vaccine—a weakened form of a bacterium used for decades against tuberculosis—to "train" the innate immune system and reverse some of the effects of aging on the brain.
In mice, this immunization successfully reprogrammed microglia, the brain's immune cells. This improved their ability to remove myelin debris, a type of waste that can accumulate with age and hinder the repair of damaged brain tissue. Thanks to this intervention, improved recovery was observed in damaged brain areas.
All of these results offer new insights into how aging affects the immune system and open the door to potential strategies for reversing decline by reprogramming the immune system.
Although senolytic vaccines open up new therapeutic possibilities, there are still significant challenges that must be addressed before their application in humans.
One of the key aspects is understanding precisely how they act. The problem is that the proteins they target can also be found, in smaller quantities, in other non-aging cells. Therefore, it is important to know whether the benefits are due only to the elimination of senescent cells or whether healthy cells with those same markers are also being eliminated.
Furthermore, the immune response must be carefully monitored. If the immune system is overactive, it can produce unwanted effects such as acute inflammation or even cytokine release syndrome, a dangerous reaction that can damage healthy tissue.
If these vaccines reach the clinical stage, it will be essential to define several factors: the appropriate dose, the frequency of administration, and how long the antibodies remain active in the body. Only then can we ensure that these vaccines are not only effective but also safe for use in humans.
Although there is still a long way to go, research marks a paradigm shift: using vaccines not only to prevent infections, but also to slow aging and its associated diseases. A medicine of the future that could be closer than we imagine.
Article published in The Conversation .
Estefanía Díaz del Cerro: Postdoctoral research associate. Collaborator with the Aging, Psychoneuroimmunoendocrinology, and Nutrition research group at the Complutense University of Madrid.
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