TY - JOUR
T1 - Accelerated aging pathology in ad libitum fed XpdTTD mice is accompanied by features suggestive of caloric restriction
AU - Wijnhoven, Susan W.P.
AU - Beems, Rudolf B.
AU - Roodbergen, Marianne
AU - Van Den Berg, Jolanda
AU - Lohman, Paul H.M.
AU - Diderich, Karin
AU - Van Der Horst, Gijsbertus T.J.
AU - Vijg, Jan
AU - Hoeijmakers, Jan H.J.
AU - Van Steeg, Harry
N1 - Funding Information:
We are very grateful to Piet de With, Gwen Intres, Conny van Oostrom, Coen Moolenbeek, Christine Soputan and Henny Loendersloot for their skilful technical assistance. This work was financially supported by National Institute of Health (NIH)/National Institute of Aging (NIA), grant number 1 PO1 AG-17242, NIEHS (1UO1 ES011044), Netherlands Organization for Scientific Research (NWO) through the foundation of the Research Institute Diseases of the Elderly, as well as grants from the Dutch Cancer Society, (EUR 99-2004) and EC (QRTL-1999-02002).
PY - 2005/11/21
Y1 - 2005/11/21
N2 - 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.
AB - 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.
KW - Accelerated aging
KW - Caloric restriction
KW - Longevity study
KW - Pathology features
KW - Xpd mice
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U2 - 10.1016/j.dnarep.2005.07.002
DO - 10.1016/j.dnarep.2005.07.002
M3 - Article
C2 - 16115803
AN - SCOPUS:27544480902
SN - 1568-7864
VL - 4
SP - 1314
EP - 1324
JO - DNA Repair
JF - DNA Repair
IS - 11
ER -