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

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• 作者：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 and Harry van Steeg
• 刊名：DNA Repair
• 出版年：2005
• 期刊代码：121_15687864
• 类别：ch
• 出版时间：2005
• 卷：4
• 期：11
• 页码：1314-1324
• 文件大小：2018 K

摘要

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. Xpd^TTD 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 Xpd^TTD 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 Xpd^TTD 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 Xpd^TTD mice to reduce metabolism (ROS production) in an attempt to extend their life span. Our current findings in Xpd^TTD mice further strengthen the link between DNA damage, repair and aging.