8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

Peter German, David Saenz, Peter Szaniszlo, Leopoldo Aguilera-Aguirre, Lang Pan, Muralidhar L. Hegde, Attila Bacsi, Gyorgy Hajas, Zsolt Radak, Xueqing Ba, Sankar Mitra, John Papaconstantinou, Istvan Boldogh

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER “wires” senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed −86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

Original languageEnglish (US)
Pages (from-to)51-65
Number of pages15
JournalMechanisms of Ageing and Development
Volume161
DOIs
StatePublished - Jan 1 2017

Keywords

  • 8-oxoguanine
  • Aging
  • OGG1
  • Senescence

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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    German, P., Saenz, D., Szaniszlo, P., Aguilera-Aguirre, L., Pan, L., Hegde, M. L., Bacsi, A., Hajas, G., Radak, Z., Ba, X., Mitra, S., Papaconstantinou, J., & Boldogh, I. (2017). 8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging. Mechanisms of Ageing and Development, 161, 51-65. https://doi.org/10.1016/j.mad.2016.06.009