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Genome Biol. 2018 Feb 16;19(1):22. doi: 10.1186/s13059-018-1397-1.

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

Author information

1
The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK. r.lowe@qmul.ac.uk.
2
The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK.
3
Kennel Club Genetics Centre, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, UK.
4
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
5
University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
6
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
7
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
8
Max Planck Institute for Informatics, Saarland Informatics Campus, Saarbr├╝cken, Germany.
9
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.
10
School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
11
Primate Genetics Laboratory, Leibniz Institute for Primate Research, German Primate Center, G├Âttingen, Germany.
12
The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK. v.rakyan@qmul.ac.uk.
13
Centre for Genomic Health, Queen Mary University of London, EC1M 6BQ, London, UK. v.rakyan@qmul.ac.uk.

Abstract

BACKGROUND:

Mammalian 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.

RESULTS:

A 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.

CONCLUSIONS:

Overall, 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.

KEYWORDS:

Ageing; Epigenetics; Methylation

PMID:
29452591
PMCID:
PMC5815211
DOI:
10.1186/s13059-018-1397-1
[Indexed for MEDLINE]
Free PMC Article

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