Conserved epigenetic hallmarks of T cell aging during immunity and malignancy.
Journal
Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306
Informations de publication
Date de publication:
12 Jun 2024
12 Jun 2024
Historique:
received:
03
04
2024
accepted:
13
05
2024
medline:
13
6
2024
pubmed:
13
6
2024
entrez:
12
6
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38867059
doi: 10.1038/s43587-024-00649-5
pii: 10.1038/s43587-024-00649-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01CA237311
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01AI144616
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01AI172607
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01AI145024
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : K08CA279926
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI146032
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : CA238439
Informations de copyright
© 2024. The Author(s).
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