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The rate of ageing-associated DNA methylation dynamics is a molecular readout of lifespan variation amongst mammalian species [TC1_450k]

ABSTRACT: We used liver samples from TC1 Mice to determine rate of change of methylation with respect to age.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE104216 | GEO | 2018/01/17

SECONDARY ACCESSION(S): PRJNA412043

REPOSITORIES: GEO

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The rate of ageing-associated DNA methylation dynamics is a molecular readout of lifespan variation amongst mammalian species [Macaque_450k]

Project description:We used blood samples from Macaque to determine rate of change of methylation with respect to age.

2018-01-17 | GSE104217 | GEO

The rate of ageing-associated DNA methylation dynamics is a molecular readout of lifespan variation amongst mammalian species [Bis-PCR: naked mole-rat]

Project description:We used liver samples from Naked Mole Rat to determine rate of change of methylation with respect to age.

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The rate of ageing-associated DNA methylation dynamics is a molecular readout of lifespan variation amongst mammalian species

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

2018-01-17 | GSE86059 | GEO

The rate of ageing-associated DNA methylation dynamics is a molecular readout of lifespan variation amongst mammalian species [Bis-PCR: dog]

Project description:We used buccal samples from two different dog breeds with well established differences in average lifespan to perform genome-scale identification of ageing-associated differentially methylated positions (aDMPs) in a total of 48 different dogs. A significant proportion of aDMPs that gained methylation with age replicated in an independent cohort. Furthermore, we also show that human aDMPs show similar ageing-associated dynamics at the homologous genomic regions in the dog. The replicated aDMPs show a faster rate of change with age in the shorter lived dog species. Strikingly, these aDMPs also show a faster rate of change with age in dogs overall compared with humans.

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Ageing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species.

Project description:BackgroundMammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species.ResultsA large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu.ConclusionsOverall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals.

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Project description: Not available

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