Universität zu Köln

Hahn, Oliver ORCID: 0000-0001-9015-4545, Stubbs, Thomas M., Reik, Wolf ORCID: 0000-0003-0216-9881, Groenke, Sebastian, Beyer, Andreas ORCID: 0000-0002-3891-2123 and Partridge, Linda ORCID: 0000-0001-9615-0094 (2018). Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity. PLoS Genet., 14 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

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Abstract

Dietary, pharmacological and genetic interventions can extend health- and lifespan in diverse mammalian species. DNA methylation has been implicated in mediating the beneficial effects of these interventions; methylation patterns deteriorate during ageing, and this is prevented by lifespan-extending interventions. However, whether these interventions also actively shape the epigenome, and whether such epigenetic reprogramming contributes to improved health at old age, remains underexplored. We analysed published, whole genome, BS-seq data sets from mouse liver to explore DNA methylation patterns in aged mice in response to three lifespan-extending interventions: dietary restriction (DR), reduced TOR signaling (rapamycin), and reduced growth (Ames dwarf mice). Dwarf mice show enhanced DNA hypermethylation in the body of key genes in lipid biosynthesis, cell proliferation and somatotropic signaling, which strongly correlates with the pattern of transcriptional repression. Remarkably, DR causes a similar hypermethylation in lipid biosynthesis genes, while rapamycin treatment increases methylation signatures in genes coding for growth factor and growth hormone receptors. Shared changes of DNA methylation were restricted to hypermethylated regions, and they were not merely a consequence of slowed ageing, thus suggesting an active mechanism driving their formation. By comparing the overlap in ageing-independent hypermethylated patterns between all three interventions, we identified four regions, which, independent of genetic background or gender, may serve as novel biomarkers for longevity-extending interventions. In summary, we identified gene body hypermethylation as a novel and partly conserved signature of lifespan-extending interventions in mouse, highlighting epigenetic reprogramming as a possible intervention to improve health at old age.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hahn, Oliver UNSPECIFIED orcid.org/0000-0001-9015-4545 UNSPECIFIED Stubbs, Thomas M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reik, Wolf UNSPECIFIED orcid.org/0000-0003-0216-9881 UNSPECIFIED Groenke, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-167297
DOI:	10.1371/journal.pgen.1007766
Journal or Publication Title:	PLoS Genet.
Volume:	14
Number:	11
Date:	2018
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7404
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR RECEPTOR-3; FATAL NEOPLASTIC DISEASES; DNA METHYLATION PATTERNS; ELEMENT-BINDING PROTEIN; INCREASE LIFE-SPAN; AMES DWARF MICE; CALORIC RESTRICTION; DIETARY RESTRICTION; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTIONAL CONTROL Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16729