Did you ever question mortality? Some people believe in the existence of living elements (like our soul), even after our death. For us biologists, there is a standard consideration of cells being mortal. In human biology, there is even a limitation of 50 – 60 divisions that cells can undergo, known as a ‘Hayflick limit’. While this phenomenon is essential to control cancerous cell growth, it is also the reason behind aging. Hayflick limit is attributed to telomere (repetitive sequence at the end of the chromosome) shortening. Telomeres, in general, protect the end of the chromosome while division is in process, so DNA would not get cut off or join other loose DNA ends. However, every time there is a division, part of the telomere gets cut off. You might have even heard of the monetization of telomeres. Some labs will (for a certain price, of course) tell you how long you would live based on your telomere length. Would you want to know? And would you ask for a cashback if you were hit by a truck while your telomeres are still pretty long?
Soerens and colleagues decided to question that theory in a very special immune cell – our cytotoxic megastar – a CD8+ T cell. Before I tell you what they did, I would like to introduce you to the three cell fates a T cell can expect: senescence, exhaustion, and death. Although, I am pretty sure you know about the last one, let me just briefly explain the first two. Cellular senescence is basically cells growing old and not dividing anymore; they can also have some impaired functions that can lead to inflammation. Moving on, cellular exhaustion is when T cells lose their license (ability) to kill. Now that we are all up to date, let’s find out what Soerens and colleagues did.
They created an experiment in which they administered boost immunization by three different antigens to mice at intervals of approximately 60 days. This process lasted for 10 years, because as time went on, the T cells never lost the ability to expand! This means that neither the age of the original population nor the number of stimulating events limits the expansion potential of T cells. Another interesting observation was that after so many divisions, cell telomere length remained the same! This indicated that these memory T cells were durable, and could perform many divisions without having a malignant transformation. Last but not the least, the researchers also demonstrated that these stimulated T cells still possessed antimicrobial activities.
This data opened the door for the unlimited expansion potential of T cells which could lead to them eventually outliving the host organisms, and maybe just as the title says, your T cells could potentially outlive you. On average, each naive CD8+ T cell could give rise to a cell volume of more than 30,000 times that of the planet Earth. Wowza! We, for sure, will still see a lot of T cell senescence, exhaustion, and death, especially during the events of chronic inflammation, but now we have knowledge that these fates could be avoidable.
This was definitely an eye-opening study and it will be even more than interesting to see this transferred to human specimens.
Soerens AG, Künzli M, Quarnstrom CF, Scott MC, Swanson L, Locquiao JJ, Ghoneim HE, Zehn D, Youngblood B, Vezys V, Masopust D. Functional T cells are capable of supernumerary cell division and longevity. Nature. 2023 Jan 18. doi: 10.1038/s41586-022-05626-9.
Article author: Ines Poljak. Ines is a Ph.D. student at King’s College. She worked at the University of Copenhangen on multiple myeloma bone disease. She worked in several clinical laboratories before committing herself completely to research.
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