Article Synopsis
- Epigenetic aging, tracked through specific modifications, shows potential links to species lifespan and is thought to operate through ‘epigenetic clocks’ across mammals.
- Research using murine models indicates that memory T cells maintain their epigenetic clocks independently of the host's age, tracking their cellular replication instead of chronological time.
- Analysis of human T cells reveals that naive T cells appear 'young' regardless of the individual's age, while T cell acute lymphoblastic leukemia in pediatric patients shows significant epigenetic aging, equivalent to about 200 years.
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Article Abstract
Chronological aging correlates with epigenetic modifications at specific loci, calibrated to species lifespan. Such 'epigenetic clocks' appear conserved among mammals, but whether they are cell autonomous and restricted by maximal organismal lifespan remains unknown. We used a multilifetime murine model of repeat vaccination and memory T cell transplantation to test whether epigenetic aging tracks with cellular replication and if such clocks continue 'counting' beyond species lifespan. Here we found that memory T cell epigenetic clocks tick independently of host age and continue through four lifetimes. Instead of recording chronological time, T cells recorded proliferative experience through modification of cell cycle regulatory genes. Applying this epigenetic profile across a range of human T cell contexts, we found that naive T cells appeared 'young' regardless of organism age, while in pediatric patients, T cell acute lymphoblastic leukemia appeared to have epigenetically aged for up to 200 years. Thus, T cell epigenetic clocks measure replicative history and can continue to accumulate well-beyond organismal lifespan.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333289 | PMC |
| http://dx.doi.org/10.1038/s43587-024-00649-5 | DOI Listing |
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