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This mechanism can prolong the lifespan
of the immune system.
A multinational team led by scientists at University College London has discovered a new mechanism that can slow and possibly even prevent normal aging of immune cells, one of
the nine "hallmarkers" of aging.
The researchers say this in vitro (cellular) discovery and validation in mice was "unexpected.
"
They believe that harnessing this mechanism may extend the lifespan of the immune system, allowing people to live healthier and longer lives, and will also be used to treat diseases
such as cancer and dementia.
Their findings were recently published in
the journal Nature Cell Biology.
Explaining the study, Dr Alessio Lanna, Emeritus Professor and first author of UCL Medical Sciences, said: "Immune cells are on high alert and ready to fight pathogens
.
To be effective, they must also persist in the body for decades – but the strategies used to enforce this lifelong protection are largely unknown
.
In this study, we sought to identify the mechanisms that confer longevity on immune system cells (i.
e.
, T cells) when the immune system develops an immune response to antigens, a foreign substance recognized by the body's defense immune surveillance mechanisms
.
”
Each chromosome has a protective cap called telomere, which is a special DNA sequence that can be repeated thousands of times
.
The sequence has two functions: first, it protects the coding region of chromosomes from damage, and second, it acts as a senescent clock, regulating the amount of
cell replication (also known as division).
T cells (a type of white blood cell or immune cell), like other cells, telomeres shorten (telomere wear)
as the cell divides.
When telomeres reach a critical length, cells stop dividing and enter senescence, a process that is processed by the immune system or persists in a changed, dysfunctional state
.
As the immune system no longer works effectively, this leads to chronic infections, cancer, and death
.
Telomere wear has been described as one of
the "signs of aging".
In this in vitro study, the researchers activated the immune response
of T lymphocytes to microbes (foreign infections).
Unexpectedly, they observed telomure transfer between
the two types of white blood cells in "extracellular vesicles" (small particles that promote cell-to-cell communication).
Antigen-presenting cells (APCs) are composed of B cells, dendritic cells, or macrophages and act as
"telomere donors" to T lymphocytes (telomure receptor cells).
After telomere metastasis, recipient T cells become long-lived, with memory and stem cell properties that allow T cells to protect their host from lethal infections
for long periods of time.
Telomere transfer reactions extend some telomeres about
30 times more than telomerase.
Telomerase is a single DNA synthesizer used to maintain telomeres in stem cells (cells of the immune system) and is found in
fetal tissue, germ cells, and sperm.
However, it does not provide this function in other cells, causing telomere wear
.
Even in immune cells that are naturally active in this enzyme, a sustained immune response leads to progressive inactivation of telomerase, resulting in telomere shortening, at which point cells stop dividing and replicating aging
occurs.
Professor Lanna added: "Telomere transfer reactions between immune cells add evidence to the Nobel Prize discovery of telomerase, showing that cells are able to regulate chromosome length
by exchanging telomeres before telomerase action begins.
It is possible to delay or cure aging
through telomere metastasis.
”
After discovering a new "anti-aging" mechanism, the same team determined that telomere extracellular vesicles can be purified from the blood and, when added to T cells, have anti-aging activity
in both human and mouse immune systems.
The researchers found (in human cells and mice) that purified extracellular vesicle preparations can be used alone or in combination with vaccines, and this prolonged sustained immune protection could, in principle, avoid the need for
revaccination.
Alternatively, the "telomere donor" transfer reaction can be directly facilitated
in the cell.
While more research is needed, the scientists say it illustrates the possibility of preventing immunoaging and new forms of
aging.
Professor Lanna concludes: "Telomere biology has been studied for more than 40 years
.
For decades, telomerase has been considered the only mechanism
responsible for telomere extension and maintenance in cells.
Our findings shed light on a different mechanism that does not require telomerase to lengthen telomeres and works when telomerase is still inactive in cells.
”
References: "An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory" by Alessio Lanna, Bruno Vaz, Clara D'Ambra, Salvatore Valvo, Claudia Vuotto, Valerio Chiurchiù, Oliver Devine, Massimo Sanchez, Giovanna Borsellino, Arne N.
Akbar, Marco De Bardi, Derek W.
Gilroy, Michael L.
Dustin, Brendan Blumer, and Michael Karin, 15 September 2022, Nature Cell Biology.
“The Hallmarks of Aging” by Carlos López-Otín, Maria A.
Blasco, Linda Partridge, Manuel Serrano and Guido Kroemer, 6 June 2013, Cell.
