Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
Por:
Anglada, T, Repulles, J, Espinal, A, LaBarge, MA, Stampfer, MR, Genesca, A, Martin, M
Publicada:
15 mar 2019
Resumen:
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 gamma H2AX foci before and after 1Gy of gamma-rays 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.
Filiaciones:
Anglada, T:
Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Bellaterra 08193, Spain
Repulles, J:
Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Bellaterra 08193, Spain
Biomed Res Inst St Pau IIB St Pau, Microscopy Platform, Barcelona 08041, Spain
Espinal, A:
Univ Autonoma Barcelona, Serv Estadist Aplicada, Bellaterra 08193, Spain
LaBarge, MA:
City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Ctr Canc & Aging, Duarte, CA 91010 USA
Lawrence Berkeley Natl Lab, Biol Syst & Engn Div, Berkeley, CA 94720 USA
Stampfer, MR:
Lawrence Berkeley Natl Lab, Biol Syst & Engn Div, Berkeley, CA 94720 USA
Genesca, A:
Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Bellaterra 08193, Spain
Martin, M:
Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Bellaterra 08193, Spain
Green Submitted, Green Published, gold
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