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Research Paper|Volume 11, Issue 13|pp 4536—4546

Spontaneous γH2AX foci in human dermal fibroblasts in relation to proliferation activity and aging

Vadim Zorin1, Anna Grekhova2,3, Margarita Pustovalova4, Alla Zorina1, Nadezhda Smetanina2, Natalia Vorobyeva2,5, Pavel Kopnin6, Ilmira Gilmutdinova7, Alexey Moskalev4,8,9, Andreyan N. Osipov2,4,5, Sergey Leonov4,10
  • 1Human Stem Cells Institute, Moscow 119333, Russia
  • 2State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow 123098, Russia
  • 3Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow 119991, Russia
  • 4Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141700, Russia
  • 5Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow 119991, Russia
  • 6N.N. Blokhin National Medical Research Oncology Center, Ministry of Health of Russia, Moscow 115478, Russia
  • 7FSBI “National Medical Research Center for Rehabilitation and Balneology”, Ministry of Health of Russia, Moscow 121099, Russia
  • 8Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology of Komi Science Center of Ural Division of Russian Academy of Sciences, Syktyvkar, Russia
  • 9Laboratory of Post-Genomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
  • 10Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia
Received: April 16, 2019Accepted: June 26, 2019Published: July 9, 2019
https://doi.org/10.18632/aging.102067

Copyright: Zorin 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.

Abstract

We assessed the effects of donor age on clonogenicity, proliferative potential, and spontaneous γH2AX foci in the proliferating (Ki67 +) and senescent (SA β-gal +) cultures of skin fibroblasts isolated from 34 donors of different age (23-82 years). Here, we demonstrated that neither the colony forming effectiveness of proliferating (Ki67+) fraction of the fibroblasts nor the average number of γH2AX foci of the same fraction does not depend on the age of the donor. The correlation between the number of γH2AX foci and the donor’s age was reliable in quiescent (Ki67-) cells. The average number of γH2AX foci in quiescent fibroblasts of donors older than 68 years was about two times higher than in the same cells of up to 30 years old donors. The number of γH2AX foci demonstrated a statistically significant positive correlation with the fraction of proliferating cells in fibroblast cultures. On average, proliferating cells have twice as many the γH2AX foci in comparison with the quiescent cells. Within a population of proliferating (Ki67+) cells, the degree of senescence correlated with a relative declining of constitutive γH2AX foci number, whereas in the population of quiescent (Ki67-) cells, it was proportional to augmenting the number of the γH2AX foci. Our data on a statistically significant (p=0.001) correlation between the age of the donor and the number of constitutive γH2AX foci in quiescent cells, could point out the ongoing DNA-damage response due in the maintenance of the senescent state of cells.