Delayed γH2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect

Teresa Anglada, Joan Repullés, Anna Espinal, Mark A. LaBarge, Martha R. Stampfer, Anna Genescà, Marta Martín

Research output: Contribution to journalArticleResearch

5 Citations (Scopus)

Abstract

© Anglada et al. Aging is a degenerative process in which genome instability plays a crucial role. To gain insight into the link between organismal aging and DNA repair capacity, we analyzed DNA double-strand break (DSB) resolution efficiency in human mammary epithelial cells from 12 healthy donors of young and old ages. The frequency of DSBs was measured by quantifying the number of γH2AX foci before and after 1Gy of γrays and it was higher in cells from aged donors (ADs) at all times analyzed. At 24 hours after irradiation, ADs retained a significantly higher frequency of residual DSBs than young donors (YDs), which had already reached values close to basal levels. The kinetics of DSB induction and disappearance showed that cells from ADs and YDs repair DSBs with similar speed, although analysis of early times after irradiation indicate that a repair defect may lie within the firing of the DNA repair machinery in AD cells. Indeed, using a mathematical model we calculated a constant factor of delay affecting aged human epithelial cells repair kinetics. This defect manifests with the accumulation of DSBs that might eventually undergo illegitimate repair, thus posing a relevant threat to the maintenance of genome integrity in older individuals.
Original languageEnglish
Pages (from-to)1501-1509
JournalAging
Volume11
DOIs
Publication statusPublished - 15 Mar 2019

Keywords

  • Aging
  • DNA damage
  • Double-strand break repair
  • Genome integrity
  • Human mammary epithelial cells
  • γH2AX

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