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

Models

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