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Gene expression responses to DNA damage are altered in human aging and in Werner Syndrome

Kasper J Kyng1, Alfred May, Tinna Stevnsner

  • 1Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.

Oncogene
|May 18, 2005
PubMed

Insights

DNA damage impacts gene expression, influencing aging and cancer. Aberrant transcriptional responses to DNA damage, particularly in Werner syndrome and older individuals, suggest a role for Werner protein in cellular stress and aging.

Area of Science:

  • Genomics
  • Molecular Biology
  • Aging Research

Background:

  • DNA damage and mutations are key drivers of cancer and aging.
  • Transcriptional regulation following DNA damage is not well understood.

Purpose of the Study:

  • To characterize gene expression changes in human fibroblasts after DNA damage induced by 4-nitroquinoline-1-oxide (4NQO), gamma-irradiation, and UV-irradiation.
  • To investigate age-associated and Werner syndrome-associated transcriptional alterations in response to DNA damage.

Main Methods:

  • Gene expression profiling of 6912 genes in human primary fibroblasts.
  • Exposure to three distinct DNA-damaging agents (4NQO, gamma-irradiation, UV-irradiation).
  • Analysis of transcriptional responses in cells from young, old, and Werner syndrome (WS) individuals.

Main Results:

  • Each stress type induced specific gene expression changes (up to 10-fold).
  • 85 genes exhibited consistent expression changes (3-40 fold) across all three stress types.
  • WS and old individuals showed similar aberrant transcriptional responses to gamma- and UV-irradiation compared to young individuals.

Conclusions:

  • Aberrant DNA damage-induced gene regulation may contribute to the aging process.
  • Werner protein appears to play a role in stress-induced gene expression, as suggested by WS and old individuals' responses.
  • Understanding these transcriptional changes offers insights into aging and premature aging conditions like WS.

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