An international team led by UCL scientists discovered a new mechanism that slows and may even prevent the natural aging of immune cells – one of the nine ‘hallmarks of ageing’.

According to research published in Nature Cell Biology, the discovery in-vitro (cells) and validation in mice was “unexpected.” The researchers believe that by using this method, the immune system might live longer and be more effective against diseases like cancer and dementia.

Dr. Alessio Lanna, the study’s lead author and an honorary professor at the UCL Division of Medicine, noted that immune cells are constantly on high alert and prepared to combat invaders. In order to be effective, they must also stay in the body for a long time. However, the methods used to carry out this lifetime protection are mainly unknown.

In this study, they wanted to understand the mechanisms that bestow lifespan to immune system cells, known as T cells, at the start of the immunological response against an antigen, a foreign substance recognized by the immune-surveillance mechanisms of the body’s defense.

Why does the immune system get older?

Every chromosome in a cell has a protective cap called a telomere, which is made up of a certain DNA sequence that is repeated thousands of times. The sequence has two functions: first, it guards the chromosomes’ coding sections and keeps them safe from harm; second, it functions as a biological clock that regulates how many replications (also known as divisions) a cell can carry out.

In T cells (a kind of white blood or immune cell) and the majority of other cells, the telomeres get shorter with each cell division (telomere attrition). When the telomeres get dangerously short, the cell stops dividing and enters senescence, when it either undergoes immune system disposal or continues to exist in an altered, dysfunctional condition.

Chronic infections, cancer, and mortality occur as a result of the immune system no longer functioning properly. Telomere attrition has been regarded as a “hallmark of ageing.”

Study results

In the study, T cells were used to start an immune response against a bacterium in vitro (foreign infection). Unexpectedly, they discovered an ‘extracellular vesicle’-based telomere transfer reaction between two different types of white blood cells (small particles that facilitate intercellular communication). To the T lymphocyte, the telomere recipient cell, an antigen-presenting cell (APC), made up of either B cells, dendritic cells, or macrophages, served as a “telomere donor.” Upon transfer of the telomeres, the recipient T cell became long-lived and possessed memory and stem cell characteristics, allowing it to provide long-term protection against a deadly infection.

Some telomeres were stretched about 30 times more by the telomere transfer reaction than by telomerase. Telomerase is the only DNA-making enzyme that helps keep telomeres in stem cells, immune system cells, fetal tissue, reproductive cells, and sperm in good shape. But it doesn’t do this in other cells, which is what causes telomere attrition. Even in immune cells where the enzyme is naturally active, ongoing immunological responses promote progressive telomerase inactivation, which results in telomere shortening, which causes replicative senescence when cells stop replicating.

“The telomere transfer reaction,” as explained by Professor Lanna, “between immune cells adds to the Nobel-prize-winning discovery of telomerase and shows that cells are capable of exchanging telomeres as a way to regulate chromosome length before telomerase action begins. It is possible that ageing may be slowed down or cured simply by transferring telomeres.”

Making use of the new mechanism

Following the discovery of the novel “anti-ageing” mechanism, the same research team demonstrated that telomere extracellular vesicles can be isolated from blood and, when combined with T cells, exhibit anti-ageing properties in both mouse and human immune systems.

Purified extracellular vesicle preparations may be provided alone or in conjunction with a vaccine, the researchers found (in human cells and animals), and these prolonged durable immune defenses, in theory, may eliminate the need for revaccination.

As an alternative, it is possible to directly stimulate the ‘telomere donor’ transfer process in cells. The experts claim that even though much more research is necessary, this shows the potential of new prophylactic (preventative) therapy for immunological senescence and aging.

“Telomere biology has been studied for more than 40 years. For decades, a single enzyme, telomerase, has been credited as the sole mechanism responsible for telomere elongation and maintenance in cells.”

“Our results,” concludes Professor Lanna, “illuminate how a different mechanism that does not require telomerase to extend telomeres and act when telomerase is still inactive in the cell.”

Source: 10.1038/s41556-022-00991-z

Image Credit: Getty

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