Early-life environmental effects on ageing in an evolutionary context

There are currently more people aged over 65 than aged under 16 living in the UK. As the elderly compose an increasing proportion of our society, understanding the basic biology of ageing becomes an urgent priority. There is astonishing variation between individuals in both ageing rates and lifespan. Understanding the causes of this variation is central to long-standing hopes of alleviating or postponing the ageing process and meeting the challenges associated with an ageing population.

In humans and other long-lived mammals, environmental conditions experienced during early life play an important role in determining health and mortality risk in adulthood. Epidemiological studies in humans show that individuals experiencing poor nutrition or infection during development or infancy have increased risk of ill health (e.g. heart disease, diabetes) and shortened life expectancy. Many researchers have suggested that these early-life environmental effects reflect developmental responses that evolved in our distant ancestors to allow individuals to grow up to ‘match’ their expected environment. Recently, there have been major advances in our understanding of the proximate physiological mechanisms linking a poor start in life with later health. However, understanding of the ultimate evolutionary mechanisms that have shaped developmental responses to the environment and their consequences for the ageing process in long-lived vertebrates has remained very limited. This is largely because modern humans and domestic and laboratory animals experience benign and protected environments that are not representative of the conditions in which life histories and ageing actually evolved.

I will address this crucial gap in our knowledge by testing how natural selection has shaped individual responses to early-life environmental conditions in mammals, using a long-term study of wild Soay sheep on St Kilda. This study population represents a unique system in which to understand the evolution of ageing in nature. Individuals in this population experience a highly variable environment and have been the subject of extremely detailed individual-based monitoring since 1985. Repeated records on individual reproductive performance, body mass and parasite burden have already been collected over the lives of more than 5,000 animals. Blood samples collected at capture as part of the study provide a remarkable, but as yet untapped, resource to assay relevant biochemical and immunological markers associated with ageing.

My overarching aim is to test and integrate evolutionary and physiological explanations for how and why early environmental conditions drive variation in ageing rates in the Soay sheep population. I will combine existing longitudinal data on environment and life history with new laboratory work using blood samples to measure immune responses and levels of cellular damage across the lifetimes of thousands of individual sheep

I will use this data to address the hypothesis that developmental responses to poor nutrition or infection in early life represent ‘predictive adaptive responses’ that allow individuals to match their expected adult environment. I will also determine how natural selection acts on the physiological trade-offs between growth, reproduction, immune responses and physiological damage in a complex and variable natural environment. Ultimately, I will quantify how, when and why natural selection favours particular developmental and life history strategies and how this influences ageing rates and lifespan.

The completed project will represent one of the most detailed longitudinal studies of the evolutionary and environmental causes of ageing ever undertaken outside of the laboratory. It will provide novel and timely tests of evolutionary predictions that could explain the effects of developmental environment, growth and infection in early life on ageing and health in later adulthood in long-lived mammals.

New insight into the way natural selection acts on immunological variation in wild vertebrate systems. Large-scale longitudinal sampling of antibody variation using blood samples collected as part of the long-term study of Soay sheep on St Kilda has provided some of the clearest evidence to date that immunological phenotypes are highly heritable in natural systems and are under complex patterns of natural section.
Developed a variety of methods for measuring telomere lengths in sheep, and applied these to wild Soay sheep on St Kilda. Initial evidence suggests strong associations between leukocyte telomere length and longevity in this system. With collaborators, I have also obtained funding – through a BBSRC International Workshop grant and a Leverhulme International Network grant – to develop a network of researchers interested in understanding variation in telomere dynamics among and within species. We have also developed methods for telomere measurement using samples from cattle and recently were awarded a BBSRC responsive mode grant to test the utility of telomere length as a biomarker in dairy cattle.