The environmental drivers of senescence: an experimental test in the wild

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

Age predicts many things about our health, including which infections we might have, our risk of dying from these infections, or which chronic diseases we are at risk from. Some individuals present an even greater risk, because they are ageing very fast, or are 'grey before their time'. But why? In humans, we have some answers: lifestyle, reproduction and infections appear to accelerate ageing. We know much less about what drives ageing and senescence in wild animals, but if we could identify the factors that cause rapid ageing in the wild, we could predict which individuals and populations are at risk.

Recently, a biomarker of age has been developed that can be used on wild animals. This technology is like rings in tree trunks, but is based on the observation that molecules called methyl groups gradually accumulate on DNA as individuals age. The number of these methyl groups turns out to accurately reflect chronological age. Importantly, individuals who are ageing rapidly have the highest methyl group counts. This study aims to identify environmental factors that cause some wild individuals to accumulate more methyl groups on their DNA. This phenomenon is named an "Epigenetic Clock", so put another way, we want to determine why some individuals have a fast-ticking clock, but others have a slow clicking clock, and so are likely to live longer.

To understand the causes of rapid ageing, it is immensely helpful to study an animal on which we can do simple yet powerful experiments. That is why we propose to study methylation in the wood mouse - an easily-captured wild mouse where we can conduct controlled experiments in the field to modify key stressors and measure their impact on the ageing rate. We will provide high quality food or drug treat (to control parasites) to half of the mice in our field locations, leaving the rest as untreated controls. To measure methylation, we will use an exciting new technology known as the multi-species methylation array that has already proven itself highly effective in other mammals. Our results will allow a better understanding of if and how nutrition and infection changes methylation to cause individuals to age faster or slower than expected. Because nutrition and infection are important to almost any animal, our work will be of interest to many researchers in ecology and 'healthy ageing' research. This will be one of the first large-scale deployments of an epigenetic clock to a wild animal, and certainly the first wild-experimental manipulation of stressors and their knock-on effects on the ageing rate.

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