Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria
Language: 
English
Abstract: 

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction.

Author(s): 
Brace, Lear E.
Vose, Sarah C.
Vargas, Dorathy F.
Zhao, Shuangyun
Wang, Xiu-Ping
Mitchell, James R.
Item Type: 
Journal Article
Publication Title: 
Aging Cell
Journal Abbreviation: 
Aging Cell
Publication Date: 
2013-12
Publication Year: 
2013
Pages: 
1144-1147
Volume: 
12
Issue: 
6
ISSN: 
1474-9726
DOI: 
10.1111/acel.12142
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23895664

Turabian/Chicago Citation

Lear E. Brace, Sarah C. Vose, Dorathy F. Vargas, Shuangyun Zhao, Xiu-Ping Wang and James R. Mitchell. 2013-12. "Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria." Aging Cell 12: 6: 1144-1147. 10.1111/acel.12142.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1111/acel.12142 | issn = 1474-9726 | volume = 12 | pages = 1144-1147 | last = Brace | first = Lear E. | coauthors = Vose, Sarah C., Vargas, Dorathy F., Zhao, Shuangyun, Wang, Xiu-Ping, Mitchell, James R. | title = Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria | journal = Aging Cell | date = 2013-12 | pmid = | pmc = }} </ref>