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DNA methylation as epigenetic clock of biological age? An experimental test in wild birds

Project description

DNA methylation as an epigenetic clock in wild birds

DNA methylation (DNAm), an epigenetic effect, has emerged as a superior marker of biological age in epidemiological studies and can predict remaining lifespans better than chronological age. The identification of factors that contribute to ageing-related methylation has therefore become important for understanding healthy ageing. The EU-funded wildEPIClock project will exploit a large existing set of biological samples from wild jackdaws (Coloeus monedula) with known life histories, monitored throughout their lives, to reveal causes and consequences of DNAm variation. The project will integrate evolutionary ecology, quantitative genetics and biomedicine to develop an epigenetic clock for understanding shifts in DNAm and their ultimate fitness consequences, unravelling extragenic mechanisms of inheritance and phenotypic evolution in an ecologically relevant setup.

Objective

DNA methylation (DNAm), an epigenetic effect, changes with age in a site-dependent way. DNAm score, integrating methylation state at many sites, has recently emerged as a superior marker of biological age in epidemiological studies: it predicts remaining lifespan markedly better than chronological age (CA). Identification of factors that contribute to ageing-related methylation has thereby become of importance for understanding healthy ageing. In this project, I will use a large existing set of biological samples of a free-ranging animal (jackdaw, Coloeus monedula) with known life-histories, monitored longitudinally throughout their lives, to reveal causes (experimental approach) and consequences (lifelong monitoring) of DNAm variation. By integrating expertise from evolutionary ecology, quantitative genetics and biomedicine, I will develop an epigenetic clock to build a comprehensive understanding of shifts in DNAm and their ultimate fitness consequences, unravelling extragenic mechanisms of inheritance and phenotypic evolution in an ecologically relevant setup. Specific objectives, implemented through dedicated work packages, are:
O1-Groundwork: Develop an epigenetic clock of CA for wild jackdaws. Method WP1: wet-lab analyses of DNAm and identification of CpG sites where methylation changes with CA to be combined in a DNAm score of age.
O2-Causes: Identify environmental and quantitative (epi)genetic causes of DNAm variation, leveraging a long-term brood size manipulation experiment that affected ageing in parents (mortality) and offspring (telomere dynamics). Method WP2: analysis of longitudinal age-corrected DNAm data and the pedigree.
O3&O4-Consequences: Study the link between the DNAm and its results on life-history traits according to the manipulation (O3,WP3a). Quantify transgenerational epigenetic inheritance (O4, WP3b). Method: longitudinal data analysis of phenotypic traits and transgenerational effects to unravel consequences of variation in DNAm.

Coordinator

RIJKSUNIVERSITEIT GRONINGEN
Net EU contribution
€ 187 572,48
Address
Broerstraat 5
9712CP Groningen
Netherlands

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Region
Noord-Nederland Groningen Overig Groningen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 187 572,48