title: Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition.
abstract: Adverse environmental exposures of mothers during fetal period predispose offspring to a range of age-related diseases earlier in life. Here, we set to determine whether a deregulated epigenetic pattern is similar in young animals whose mothers' nutrition was modulated during fetal growth to that acquired during normal aging in animals. Using a rodent model of maternal undernutrition (UN) or overnutrition (ON), we examined cytosine methylation profiles of liver from young female offspring and compared them to age-matched young controls and aged (20-month-old) animals. HELP-tagging, a genomewide restriction enzyme and sequencing assay demonstrates that fetal exposure to two different maternal diets is associated with nonrandom dysregulation of methylation levels with profiles similar to those seen in normal aging animals and occur in regions mapped to genes relevant to metabolic diseases and aging. Functional consequences were assessed by gene expression at 9 weeks old with more significant changes at 6 months of age. Early developmental exposures to unfavorable maternal diets result in altered methylation profiles and transcriptional dysregulation in Prkcb, Pc, Ncor2, and Smad3 that is also seen with normal aging. These Notch pathway and lipogenesis genes may be useful for prediction of later susceptibility to chronic disease.
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Heo
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Tozour
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.|Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Delahaye
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Lingguang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.|Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.|Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Francine Hughes
authors.initials: FH
authors.lastname: Einstein
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D056726:Genetic Association Studies; D016678:Genome; D008099:Liver / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D044342:Malnutrition / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D017207:Rats, Sprague-Dawley
keywords: DNA methylation; aging; liver; maternal overnutrition; maternal undernutrition