Research Paper Volume 11, Issue 5 pp 1510—1523
Delayed γH2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
- 1 Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
- 2 Microscopy Platform, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, 08041, Spain
- 3 Servei d’Estadística Aplicada, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
- 4 Department of Population Sciences, and Center for Cancer and Aging, Beckman Research Institute at City of Hope, Duarte, CA, 91010, USA
- 5 Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
- 6 Equal contribution
received: September 16, 2018 ; accepted: March 9, 2019 ; published: March 14, 2019 ;https://doi.org/10.18632/aging.101849
How to Cite
Copyright: Anglada et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 γ-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.