Early age decline in DNA repair capacity in the liver: In depth profile of differential gene expression

Avital Guedj, Anat Geiger-Maor, Eithan Galun, Hagai Amsalem, Jacob Rachmilewitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Aging is associated with progressive decline in cell function and with increased damage to macromolecular components. DNA damage, in the form of double-strand breaks (DSBs), increases with age and in turn, contributes to the aging process and age-related diseases. DNA strand breaks triggers a set of highly orchestrated signaling events known as the DNA damage response (DDR), which coordinates DNA repair. However, whether the accumulation of DNA damage with age is a result of decreased repair capacity, remains to be determined. In our study we showed that with age there is a decline in the resolution of foci containing γH2AX and pKAP-1 in diethylnitrosamine (DEN)-treated mouse livers, already evident at a remarkably early age of 6-months. Considerable age-dependent differences in global gene expression profiles in mice livers after exposure to DEN, further affirmed these age related differences in the response to DNA damage. Functional analysis identified p53 as the most overrepresented pathway that is specifically enhanced and prolonged in 6- month-old mice. Collectively, our results demonstrated an early decline in DNA damage repair that precedes 'old age', suggesting this may be a driving force contributing to the aging process rather than a phenotypic consequence of old age.

Original languageEnglish
Pages (from-to)3131-3146
Number of pages16
JournalAging
Volume8
Issue number11
DOIs
StatePublished - 2016
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported in part by the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation.

Keywords

  • Aging
  • DNA repair
  • KAP-1
  • P 53
  • RNAseq
  • γH2AX

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