Aging

DNA Damage and Aging

Science's STKE  21 May 2002:
Vol. 2002, Issue 133, pp. TW181
DOI: 10.1126/stke.2002.133.TW181

Abstract

A popular theory postulates that aging is triggered by cellular accumulation of oxidative damage. The causal role of oxidative DNA damage in aging is strongly supported in a study by de Boer et al. (see the Perspective by Hasty and Vijg) of mice carrying a mutant version of the DNA helicase gene XPD. This gene causes the rare human disorder trichothiodystrophy (TTD). The XPD mutant mice, which are severely impaired in transcription-coupled repair and mildly impaired in nucleotide-excision repair, exhibited many symptoms of premature aging, including osteoporosis, infertility, early graying, and reduced life-span. Mice doubly mutant for XPD and a second gene required for nucleotide-excision repair, XPA, showed greatly accelerated aging that correlated with an increased cellular sensitivity to oxidative DNA damage. The authors propose that the aging phenotype in the TTD mice is caused by unrepaired DNA damage that compromises transcription, which in turn leads to functional inactivation of critical genes and cell death.

J. de Boer, J. O. Andressoo, J. de Wit, J. Huijmans, R. B. Beems, H. van Steeg, G. Weeda, G. T. J. van der Horst, W. van Leeuwen, A. P. N. Themmen, M. Meradji, J. H. J. Hoeijmakers, Premature aging in mice deficient in DNA repair and transcription. Science 296, 1276-1279 (2002). [Abstract] [Full Text]

P. Hasty, J. Vijg, Genomic priorities in aging. Science 296, 1250-1251 (2002). [Summary] [Full Text]