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Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions (WGBS 1)

ABSTRACT: Investigation into changes in the methylome in young (2 months) and aged (22 months) Ames dwarf (Prop1 Hom) and WT (Prop1 Het) mice

ORGANISM(S): Mus musculus

PROVIDER: GSE89273 | GEO | 2017/02/16

SECONDARY ACCESSION(S): PRJNA351226

REPOSITORIES: GEO

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Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions (RNA-Seq)

Project description:Investigation into changes in the methylome in young (2 months) and aged (22 months) Ames dwarf (Prop1 Hom) and WT (Prop1 Het) mice

2017-02-16 | GSE89272 | GEO

Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-02-16 | GSE89275 | GEO

Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions.

Project description:BackgroundAge-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging "clock", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin.ResultsIn wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice.ConclusionsAge-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock.

| S-EPMC5370462 | biostudies-literature

Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions (WGBS 2)

Project description:Investigation into changes in the methylome in rapamycin and caloric restriction in aged mice.

2017-02-16 | GSE89274 | GEO

Transcription profiling of mouse liver from long lived Prop-1 mutant (Ames) vs. wild type controls

Project description:To compare and contrast genetic signatures from livers of young and aged Ames dwarf mice with their wild type controls. SUBMITTER_CITATION: W. H. Boylston, James H. DeFord, John Papaconstantinou (2006) Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice Age 28:125-144 Experiment Overall Design: 25 micrograms of liver RNA was isolated from young (5 dwarfs, 5 wildtype), middle aged (5 dwarfs, 5 wild type) and aged (5 dwarf, 6 wild type) mice for use in hybridization of Affymetrix gene chips according to Affymetrix protocols.

2008-06-12 | E-GEOD-3150 | biostudies-arrayexpress

Aging Liver Profiles of the Long Lived Prop-1 Mutant Mouse (Ames) and Wild Type Controls

Project description:To compare and contrast genetic signatures from livers of young and aged Ames dwarf mice with their wild type controls. Keywords: Time Course

2005-08-18 | GSE3150 | GEO

Transcription profiling of long-lived Ames dwarf mice investigating the loss of liver sexual dimorphism

Project description:Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice.

2005-05-30 | E-MEXP-347 | biostudies-arrayexpress

Normal Ad Libitum

Project description:Female Ames dwarf mouse (+/+ or +/df) with ad libitum access to water and standard pelleted food (LabDiet, PMI Feeds, Inc., St Louis, MO) caged with microisolator filter tops. Mice were killed between 24 to 26 months of age, tissues removed, rapidly frozen on dry ice, and stored in liquid nitrogen. Total liver RNA was isolated from frozen tissue as described (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). mRNA levels were measured using the Affymetrix mouse U74Av2 array according to standard protocols. After hybridization, arrays were scanned using a Hewlett-Packard GeneArray Scanner. Image analysis was performed as described (Cao SX, Dhahbi JM, Mote PL, and Spindler SR. Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice. Proc Natl Acad Sci U S A 98: 10630-10635, 2001). A more detailed description of the methods can be found in (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). Keywords = Ames dwarf Keywords = mouse Keywords = Affymetrix Keywords = caloric restriction Keywords: parallel sample

2005-01-10 | GSE1088 | GEO

Dwarf Ad libitum

Project description:Female Ames dwarf mouse (df/df) with ad libitum access to water and standard pelleted food (LabDiet, PMI Feeds, Inc., St Louis, MO) caged with microisolator filter tops. Mice were killed between 24 to 26 months of age, tissues removed, rapidly frozen on dry ice, and stored in liquid nitrogen. Total liver RNA was isolated from frozen tissue as described (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). mRNA levels were measured using the Affymetrix mouse U74Av2 array according to standard protocols. After hybridization, arrays were scanned using a Hewlett-Packard GeneArray Scanner. Image analysis was performed as described (Cao SX, Dhahbi JM, Mote PL, and Spindler SR. Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice. Proc Natl Acad Sci U S A 98: 10630-10635, 2001). A more detailed description of the methods can be found in (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). Keywords = Ames dwarf Keywords = mouse Keywords = Affymetrix Keywords = caloric restriction Keywords: parallel sample

2005-01-10 | GSE1086 | GEO

DNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation [WGBS_Mm]

Project description:The crosstalk between H3K4 monomethylation and DNA methylation has been receiving little attention to date. We investigated a mouse model harboring a loss-of-function mutation of lysine methyltransferase 2D (KMT2D), which catalyzes the monomethylation of lysine 4 on histone H3. We performed H3K4me1 ChIP-seq in spleen B cells with the wild type (WT) KMT2D as well as heterozygous (HET) and homozygous (HOM) chr15: 98,835,228 A>T KMT2D mutation. Alongside, using WGBS, we performed genome-wide DNA methylation profiling in spleen B cells with the WT KMT2D as well as HET and HOM chr15: 98,835,228 A>T KMT2D mutation.

2019-01-23 | GSE104781 | GEO

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