DNA-methylation as an epigenetic clock of biological age: A new tool to study ageing and ecology & evolution of life histories?

Understanding the root cause of ageing and associated diseases is one of the major contemporary challenges of the life sciences. Individuals with the same chronological age have been found to display enormous variation in their biological age. The assessment of an individual’s biological age is therefore a vital step towards a better understanding of the ageing process, yet developing a comprehensive biomarker has proven difficult. DNA methylation (DNAm) at many genes changes with age, and recently developed compound DNAm scores correlate strongly with chronological age in humans and a few other organisms. Importantly, individuals with a high DNAm score for their age appear to have a higher biological age, as e.g. evidenced by a higher mortality in humans. However, there have been no experimental studies investigating whether manipulations that are known to affect ageing similarly affect DNAm dynamics. Using stored longitudinal blood samples from two long-term experiments that accelerated ageing, the project aims to develop a novel DNAm score as a robust predictor of biological age of zebra finches. How DNAm scores are affected by developmental conditions, manipulated foraging conditions and investment in reproduction as well as how they relate to age-dependent mortality rate will be investigated along with the effect of sex and the heritability of site-specific DNAm patterns. The project will provide the foundation for further study of age‐related DNAm in non‐mammalian vertebrates and serve as a step towards unravelling the fundamental ageing process through identification of signature genes of biological age. It will also enable the elemental completion of an ongoing zebra finch sister experiment in the Adaptive Life program, extending it to cover the full life span of the experimental individuals.