DNA damage recognition and repair capacities in human naïve and memory T cells from peripheral blood of young and elderly subjects

Salvatore Scarpaci, Daniela Frasca, Paola Barattini, Luisa Guidi, Gino Doria

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

T cells accumulate genetic damage over time but naïve cells display higher genomic stability and longer lifespan as compared to memory cells. We found in naïve and memory T cells from young and elderly subjects that DNA damage in unirradiated cells is higher in memory than in naïve T cells, and is increased by radiation in both cell types. Repair of the radiation-induced DNA damage was much higher in naïve than in memory T cells from young subjects but null in both cell types from elderly subjects. Molecular mechanisms involved in DNA damage recognition and repair were analyzed in both cell subsets from young subjects. The intracellular distribution and amount of the DNA-dependent protein kinase (DNA-PK) complex components (ku 70, ku 80, DNA-PKcs), which are involved in the recognition and repair of DNA breaks caused by ionizing radiations, V(D)J recombination and isotype switching, was assessed in naïve and memory T cells from young subjects. While the expression of ku 70 and ku 80 was at comparable levels in both T cell subsets, DNA-PKcs, phosphorylated ku 80, and DNA-binding of ku 70/80 were mostly evident in naïve but negligible or absent in memory T cells. These findings may account for the higher genomic stability and longer lifespan of naïve as compared to memory human T cells from young subjects.

Original languageEnglish (US)
Pages (from-to)517-524
Number of pages8
JournalMechanisms of Ageing and Development
Volume124
Issue number4
DOIs
StatePublished - Apr 1 2003

Keywords

  • CD45 RA
  • CD45 RO
  • DNA repair
  • DNA-PK complex

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

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