LONDON — An international team has discovered a mechanism that may prevent human immune cells from aging. Researchers at University College London say the “unexpected” breakthrough could help scientists extend lifespans and ward off age-related diseases such as cancer and dementia.
The natural aging of immune cells is one of the nine “hallmarks of aging,” according to the team. During their study, they discovered a unique process that slows down this natural deterioration.
“Immune cells are on constant high-alert, always ready to fight pathogens. To be effective they also must persist for decades in the body – but the strategies employed to execute this life-long protection are largely unknown,” says lead author Dr. Alessio Lanna, an honorary professor at UCL Division of Medicine, in a media release.
“In this research, we sought to find out what mechanisms exist to confer longevity to immune system cells, known as T cells, at the initiation of the immune response against an antigen – a foreign substance recognized by the immune-surveillance mechanisms of defense of the body.”
Immune cells age just like the rest of the body
Study authors explain that all cells contain protective caps called telomeres. Along with protecting the chromosomes, telomeres also act as an “aging clock” which controls the number of times a cell can replicate or divide.
For specialized immune cells (T cells), telomeres get shorter and shorter with every cell division and as a person grows older. Once they reach their end, the immune cell enters a period called senescence, where the immune system either disposes of it or the T cell lives on in a dysfunctional state.
If the dysfunctional carries on however, it can lead to the onset of chronic diseases and infections, including cancer. Researchers note that telomere attrition is another one of the hallmarks of aging.
In the new study, the team triggered an immune response by T-lymphocytes against a foreign infection. To their surprise, they discovered a “telomere transfer reaction” between two types of white blood cells — in “extracellular vesicles.” These are tiny particles that handle communication between cells.
An antigen presenting cell (APC) — which consists of either B “memory” cells, dendritic cells, or macrophages — acted as a “telomere donor” for the T-lymphocyte. After the transfer, the recipient T cell lived longer and also displayed more memory and stem cell attributes. All of this helped the improved cell fight off more lethal infections over the long haul.
Even more beneficial than stem cell treatments?
Overall, scientists found that the telomere transfer reaction extended certain telomeres by about 30 times more than the benefits of telomerase.
Telomerase is a single DNA synthesizing enzyme that performs telomere maintenance in stem cells, commonly found in fetal tissue, reproductive cells, and sperm. Unfortunately, it does not provide the same benefits for other cells, which is why people suffer from telomere attrition as they grow older.
“The telomere transfer reaction 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,” Prof. Lanna explains.
How can scientists turn this into an anti-aging drug?
The team believes they can purify the telomere extracellular vesicles from the blood and add them to T cells. Doing this may trigger anti-aging activities for both mice and humans.
During the study, the team found that they could administer the purified vesicles alone or in combination with a vaccine to extend the longevity of the immune system.
Researchers also found that they could directly boost the “telomere donor” transfer reaction in cells.
“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 illuminate how a different mechanism that does not require telomerase to extend telomeres and act when telomerase is still inactive in the cell,” Prof. Lanna concludes.
The study is published in the journal Nature Cell Biology.