Reference SummaryWijnhoven SW, DNA Repair (Amst) 2005 Nov 21;4(11):1314-24
Title |
Accelerated aging pathology in ad libitum fed Xpd(TTD) mice is accompanied by features suggestive of caloric restriction. |
Authors |
Wijnhoven SW; Beems RB; Roodbergen M; van den Berg J; Lohman PH; Diderich K; van der Horst GT; Vijg J; Hoeijmakers JH; van Steeg H |
Journal |
DNA Repair (Amst) |
Volume |
4 |
Issue |
11 |
Year |
2005 |
Pages |
1314-24 |
Abstract |
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. |
Links |
J:104017 – MGI References 16115803 – National Library of Medicine/PubMed |
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6NHsd | Adrenal gland - Medulla pheochromocytoma | Adrenal gland - Medulla |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Adrenal gland - Medulla pheochromocytoma | Adrenal gland - Medulla |
8.57 |
||
C57BL/6NHsd | Blood vessel hemangioma | Blood vessel |
5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Blood vessel hemangioma | Blood vessel |
8.57 |
||
C57BL/6NHsd | Blood vessel hemangiosarcoma | Blood vessel |
2.5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Blood vessel hemangiosarcoma | Blood vessel |
2.86 |
||
C57BL/6NHsd | Bone osteosarcoma | Bone |
5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Bone osteosarcoma | Bone |
0 |
||
C57BL/6NHsd | Eye - Harderian gland adenoma | Eye - Harderian gland |
2.5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Eye - Harderian gland adenoma | Eye - Harderian gland |
0 |
||
C57BL/6NHsd | Head squamous cell carcinoma | Head |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Head squamous cell carcinoma | Head |
2.86 |
||
C57BL/6NHsd | Intestine - Small Intestine - Duodenum hyperplasia - atypical | Intestine - Small Intestine - Duodenum |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Intestine - Small Intestine - Duodenum hyperplasia - atypical | Intestine - Small Intestine - Duodenum |
17.6 |
||
C57BL/6NHsd | Intestine - Small Intestine - Duodenum hyperplasia - atypical - epithelial | Intestine - Small Intestine - Duodenum |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Intestine - Small Intestine - Duodenum hyperplasia - atypical - epithelial | Intestine - Small Intestine - Duodenum |
observed |
||
C57BL/6NHsd | Intestine - Small Intestine - Duodenum tumor | Intestine - Small Intestine - Duodenum |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Intestine - Small Intestine - Duodenum tumor | Intestine - Small Intestine - Duodenum |
0 |
||
C57BL/6NHsd | Leukocyte - Lymphocyte lymphoma | (Unspecified organ) |
25 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Leukocyte - Lymphocyte lymphoma | (Unspecified organ) |
8.57 |
||
C57BL/6NHsd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | (Unspecified organ) |
7.5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | (Unspecified organ) |
8.57 |
||
C57BL/6NHsd | Liver hepatocellular adenoma | Liver |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Liver hepatocellular carcinoma | Liver |
2.86 |
||
C57BL/6NHsd | Lung carcinoma - bronchioalveolar | Lung |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Lung carcinoma - bronchioalveolar | Lung |
2.86 |
||
C57BL/6NHsd | Mesodermal cell/mesoblast sarcoma | Liver |
2.5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Mesodermal cell/mesoblast sarcoma | Liver |
0 |
||
C57BL/6NHsd | Muscle - Smooth - Intestinal leiomyosarcoma | Intestine - Small Intestine |
2.5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Muscle - Smooth - Intestinal leiomyosarcoma | Intestine - Small Intestine |
0 |
||
C57BL/6NHsd | Pituitary gland - Pars distalis adenoma | Pituitary gland - Pars distalis |
50 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Pituitary gland - Pars distalis adenoma | Pituitary gland - Pars distalis |
8.57 |
||
C57BL/6NHsd | Pituitary gland adenoma | Pituitary gland |
51.3 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Pituitary gland adenoma | Pituitary gland |
8.6 |
||
C57BL/6NHsd | Skin - Melanocyte melanoma - benign | Skin - Melanocyte |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Skin - Melanocyte melanoma - benign | Skin - Melanocyte |
2.86 |
||
C57BL/6NHsd | Skin hyperplasia - sebaceous | Skin |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Skin hyperplasia - sebaceous | Skin |
observed |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Skin lesion | Skin |
observed |
||
C57BL/6NHsd | Skin lesion | Skin |
0 |
||
C57BL/6NHsd | Thyroid gland - Follicular cell adenoma | Thyroid gland - Follicular cell |
2.5 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Thyroid gland - Follicular cell adenoma | Thyroid gland - Follicular cell |
5.71 |
||
C57BL/6NHsd | Thyroid gland - Follicular cell hyperplasia | Thyroid gland - Follicular cell |
21.6 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | Thyroid gland - Follicular cell hyperplasia | Thyroid gland - Follicular cell |
5.9 |
||
C57BL/6NHsd | (Unspecified organ) lesion | (Unspecified organ) |
0 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | (Unspecified organ) lesion | (Unspecified organ) |
observed |
||
C57BL/6NHsd | (Unspecified organ) neoplasm | (Unspecified organ) |
35 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | (Unspecified organ) neoplasm | (Unspecified organ) |
20 |
||
C57BL/6NHsd | (Unspecified organ) tumor | (Unspecified organ) |
75 |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | (Unspecified organ) tumor | (Unspecified organ) |
54.29 |
||
C57BL/6NHsd | (Unspecified organ) tumor - benign | (Unspecified organ) |
observed |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | (Unspecified organ) tumor - benign | (Unspecified organ) |
observed |
||
C57BL/6NHsd | (Unspecified organ) tumor - malignant | (Unspecified organ) |
observed |
||
B6.129P2-Ercc2tm2(ERCC2)Jhjh | (Unspecified organ) tumor - malignant | (Unspecified organ) |
observed |