Open AccessLifespan extension by dietary intervention in a mouse model of C ockayne S yndrome uncouples early postnatal development from segmental progeria
Author(s) -
Brace Lear E.,
Vose Sarah C.,
Vargas Dorathy F.,
Zhao Shuangyun,
Wang XiuPing,
Mitchell James R.
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12142
Subject(s) - progeria , weaning , biology , premature aging , lipodystrophy , cockayne syndrome , penetrance , physiology , endocrinology , medicine , genetics , phenotype , nucleotide excision repair , virus , gene , antiretroviral therapy , viral load , dna repair
Summary 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.