Accelerated aging pathology in ad libitum fed Xpd(TTD) mice is accompanied by features suggestive of caloric restriction.
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.
Wijnhoven
Susan W P
SW
National Institute of Public Health and the Environment, Laboratory of Toxicology, Pathology and Genetics, Bilthoven, The Netherlands.
Beems
Rudolf B
RB
Roodbergen
Marianne
M
van den Berg
Jolanda
J
Lohman
Paul H M
PH
Diderich
Karin
K
van der Horst
Gijsbertus T J
GT
Vijg
Jan
J
Hoeijmakers
Jan H J
JH
van Steeg
Harry
H
D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001835:Body Weight / Q000235:genetics; D031204:Caloric Restriction / Q000401:mortality; D016923:Cell Death / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009929:Organ Size / Q000235:genetics; D010641:Phenotype; D011897:Random Allocation; D054463:Trichothiodystrophy Syndromes / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D051759:Xeroderma Pigmentosum Group D Protein / Q000172:deficiency* / Q000235:genetics*
D051759:Xeroderma Pigmentosum Group D Protein; C497293:Ercc2 protein, mouse