Accelerated aging pathology in ad libitum fed XpdTTD mice is accompanied by features suggestive of caloric restriction

Susan W.P. Wijnhoven, Rudolf B. Beems, Marianne Roodbergen, Jolanda Van Den Berg, Paul H.M. Lohman, Karin Diderich, Gijsbertus T.J. Van Der Horst, Jan Vijg, Jan H.J. Hoeijmakers, Harry Van Steeg

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Trichothiodystrophy (TTD) patients with a mutation in the XPD gene of nucleotide excision repair (NER) have a short life span and show various features of premature aging, thereby linking DNA damage to the aging process. XpdTTD mutant mice share many features with TTD patients, including a shorter life span, accompanied by a segmental progeroid phenotype. Here we report new pathology features supportive to the premature aging phenotype of XpdTTD mice. Strikingly, accelerated aging pathology is accompanied by signs suggestive of caloric restriction (CR), a condition usually linked to retardation of age-related pathology and life extension. Accelerated aging symptoms in XpdTTD mice are most likely due to accumulation of endogenously generated DNA damage and compromised transcription leading to cell death, whereas CR symptoms may reflect the need of XpdTTD mice to reduce metabolism (ROS production) in an attempt to extend their life span. Our current findings in XpdTTD mice further strengthen the link between DNA damage, repair and aging.

Original languageEnglish (US)
Pages (from-to)1314-1324
Number of pages11
JournalDNA Repair
Volume4
Issue number11
DOIs
StatePublished - Nov 21 2005
Externally publishedYes

Keywords

  • Accelerated aging
  • Caloric restriction
  • Longevity study
  • Pathology features
  • Xpd mice

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Wijnhoven, S. W. P., Beems, R. B., Roodbergen, M., Van Den Berg, J., Lohman, P. H. M., Diderich, K., Van Der Horst, G. T. J., Vijg, J., Hoeijmakers, J. H. J., & Van Steeg, H. (2005). Accelerated aging pathology in ad libitum fed XpdTTD mice is accompanied by features suggestive of caloric restriction. DNA Repair, 4(11), 1314-1324. https://doi.org/10.1016/j.dnarep.2005.07.002