Universität zu Köln

Hahn, Oliver ORCID: 0000-0001-9015-4545, Groenke, Sebastian, Stubbs, Thomas M., Ficz, Gabriella, Hendrich, Oliver, Krueger, Felix ORCID: 0000-0002-5513-3324, Andrews, Simon, Zhang, Qifeng, Wakelam, Michael J., Beyer, Andreas ORCID: 0000-0002-3891-2123, Reik, Wolf and Partridge, Linda ORCID: 0000-0001-9615-0094 (2017). Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism. Genome Biol., 18. LONDON: BMC. ISSN 1474-760X

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Abstract

Background: 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. Results: 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. Conclusions: 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hahn, Oliver UNSPECIFIED orcid.org/0000-0001-9015-4545 UNSPECIFIED Groenke, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Stubbs, Thomas M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ficz, Gabriella UNSPECIFIED UNSPECIFIED UNSPECIFIED Hendrich, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Felix UNSPECIFIED orcid.org/0000-0002-5513-3324 UNSPECIFIED Andrews, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Qifeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Wakelam, Michael J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Reik, Wolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236277
DOI:	10.1186/s13059-017-1187-1
Journal or Publication Title:	Genome Biol.
Volume:	18
Date:	2017
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1474-760X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CALORIC RESTRICTION; GENE-EXPRESSION; LIFE-SPAN; GENOME BROWSER; CHROMATIN; MECHANISMS; LANDSCAPE; SREBP; MICE; RNA Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23627