T cells have the potential to live for a very long time – but their ageing may accelerate when a patient has leukaemia, according to a groundbreaking new study.
Researchers in the USA have unveiled new findings about the ageing process of T cells, suggesting it is very different to that of other cells.
The findings, reported in Nature Aging, come from a study of the cells’ “epigenetic clock”, measured through DNA methylation. The research involved scientists in Tennessee and Minnesota.
The project began with laboratory studies of mice at the University of Minnesota where researcher Dr David Masopust found that T cells could survive being transplanted through several animal life cycles – showing that the T cells have a lifespan that far exceeds their hosts.
Study co-leader Dr Ben Youngblood said: “Humans don't live forever. But in this case, we could test that concept for T cells. Is there an end to an epigenetic clock? Does it plateau? And it didn't for up to four lifetimes, it just kept counting, which was incredible. These cells are not bound by the reasonable limits of organism lifespan.”
This led to further studies at St Jude’s Children's Hospital, Memphis, Tennessee. The researchers found that in children with T-cell acute lymphoblastic leukaemia, T cells proved less resilient, ageing by between 100 and 200 years during the course of the disease. They believe this could lead to further insights into the disease, and find way to halt or reverse this ageing process in leukaemic T cells.
Dr Youngblood said: “We were able to use this as a subtraction model from all other programs in leukaemia to identify ones that are associated with normal ageing and proliferation versus ones that are distinct to leukaemia.
“We gained a better idea of which epigenetic programs are associated with leukaemia and which are just normal hyperproliferation and ageing.”
Source:
Mi T, Soerens AG, Alli S, Kang TG, Vasandan AB, Wang Z, Vezys V, Kimura S, Iacobucci I, Baylin SB, Jones PA, Hiner C, Mueller A, Goldstein H, Mullighan CG, Zebley CC, Masopust D, Youngblood B. (2024) “Conserved epigenetic hallmarks of T-cell aging during immunity and malignancy.” Nature Aging, 12 June 2024, doi: 10.1038/s43587-024-00649-5.
Link: https://www.nature.com/articles/s43587-024-00649-5
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