title: Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism.
abstract: Dietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during aging and extends lifespan in diverse species, including rodents. However, the mechanisms by which DR interacts with the aging process to improve health in old age are poorly understood. DNA methylation could play an important role in mediating the effects of DR because it is sensitive to the effects of nutrition and can affect gene expression memory over time.
  
  
  
  Here, we profile genome-wide changes in DNA methylation, gene expression and lipidomics in response to DR and aging in female mouse liver. DR is generally strongly protective against age-related changes in DNA methylation. During aging with DR, DNA methylation becomes targeted to gene bodies and is associated with reduced gene expression, particularly of genes involved in lipid metabolism. The lipid profile of the livers of DR mice is correspondingly shifted towards lowered triglyceride content and shorter chain length of triglyceride-associated fatty acids, and these effects become more pronounced with age.
  
  
  
  Our results indicate that DR remodels genome-wide patterns of DNA methylation so that age-related changes are profoundly delayed, while changes at loci involved in lipid metabolism affect gene expression and the resulting lipid profile.
authors.affiliation: Max Planck Institute for Biology of Ageing, 50931, Cologne, Germany.|Cellular Networks and Systems Biology, CECAD, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne, 50931, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hahn
authors.affiliation: Max Planck Institute for Biology of Ageing, 50931, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grönke
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stubbs
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ficz
authors.affiliation: Max Planck Institute for Biology of Ageing, 50931, Cologne, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hendrich
authors.affiliation: Bioinformatics Group, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Felix
authors.initials: F
authors.lastname: Krueger
authors.affiliation: Bioinformatics Group, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Andrews
authors.affiliation: Inositide Lab, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Inositide Lab, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wakelam
authors.affiliation: Cellular Networks and Systems Biology, CECAD, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne, 50931, Germany. andreas.beyer@uni-koeln.de.|Center for Molecular Medicine Cologne, University of Cologne, Cologne, 50931, Germany. andreas.beyer@uni-koeln.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyer
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK. wolf.reik@babraham.ac.uk.|The Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK. wolf.reik@babraham.ac.uk.
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
authors.affiliation: Max Planck Institute for Biology of Ageing, 50931, Cologne, Germany. Partridge@age.mpg.de.|Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK. Partridge@age.mpg.de.
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D004032:Diet; D044127:Epigenesis, Genetic; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D051379:Mice; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D005227:Fatty Acids