Julian West
posted 8 months ago

Desperately short telomeres? Alternate way to elongate them!

Once in a while, a paper gives a feeling of "Wow, at a junction in History!" Such is a recent entry in Nature Cell Biology, which I will liken to a play:

Prelude - Telomere (DNA protective caps) shortening : one of the first recognized "hallmarks of aging"... (general background from NIH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/)

Conflict - Deep unease at being at the apparent mercy of telomerase, seemingly the only enzyme that could counteract that shortening.

Resolution - Surrounded by shortening telomeres? Inadequate supply of telomerase? The "cavalry arrives", in the form of re-inforcements from other cells! This natural process (something of a cell-to-cell "transplant") was discovered in immune cells.

The Sept. 2022 article, by prof. Alessio Lanna at UCL (UK) et al.: "An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory"

A news report from UCL: https://www.ucl.ac.uk/news/2022/sep/new-mechanism-extends-life-immune-system

How does it work?

The mechanism involves immune cells called APCs (antigen-presenting cells: https://en.wikipedia.org/wiki/Antigen-presenting_cell). They play the role of the "cavalry".

The receivers of assistance from this mechanism are some T cells, a key player of the immune system.

Upon contact between the 2 cells, the donor (APC) degrades its shelterin (a protein complex protecting its telomeres), letting its telomeres to be cleaved, packed into extracellular vesicles (akin to "shipping boxes"), and basically "transplanted" to the recipient cells (i.e. the T cells), lengthening their telomeres by an average of ~3,000 base pairs.

All said and done, the "telomere-acquiring T cells are protected from senescence before clonal division begins, conferring long-lasting immune protection."

Awesome to have an alternate mechanism to telomerase: " The telomere transfer reaction extended certain telomeres about 30 times more than extension exerted by telomerase. "

Not completely surprising to find it in T cells: after all, to be effective, T cells must persist for decades in the body - carrying memories of old infections to be on guard against.

Could this mechanism be therapeutically applied to other cells in risk of entering senescence from telomere shortening?

The same research team established that those telomere extracellular vesicles ("the shipping boxes") mentioned above can be purified from the blood, and, when added to T cells, they "present anti-ageing activities in immune systems from both humans and mice."

In principle, this might end up being a "new form of prophylactic (preventative) therapies of immune senescence and age." Stay tuned!

Keith Loritz7 months ago

Hi Julian, Thanks for the writeup and links!

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