Sci. Aging Knowl. Environ., 17 April 2002
Premature Aging in Mice Deficient in DNA Repair and Transcription
Jan de Boer, Jaan Olle Andressoo, Jan de Wit, Jan Huijmans, Rudolph B. Beems, Harry van Steeg, Geert Weeda, Gijsbertus T. J. van der Horst, Wibeke van Leeuwen, Axel P. N. Themmen, Morteza Meradji, and Jan H. J. Hoeijmakershttp://sageke.sciencemag.org/cgi/content/abstract/sageke;2002/15/or5
Abstract: Science 11 April 2002 (10.1126/science.1070174) (Science Express Reports)
One theory on aging involves accumulation of DNA damage. Here we provide strong support for this hypothesis by studying mice with a mutation in XPD, a gene encoding a DNA helicase that functions in both repair and transcription and that is mutated in the human disorder trichothiodystrophy (TTD). The TTD mice were found to exhibit many symptoms of premature aging, including osteoporosis and kyphosis, osteosclerosis, early greying, cachexia, infertility, and reduced life-span. TTD mice carrying an additional mutation in XPA, which enhances the repair defect, showed a greatly accelerated aging phenotype that correlated with an increased cellular sensitivity to oxidative DNA damage. We hypothesize that aging in the TTD mice is caused by unrepaired DNA damage that compromises transcription, leading to functional inactivation of critical genes and apoptosis.
Science of Aging Knowledge Environment. ISSN 1539-6150