A bird’s DNA clock ticks faster when it faces pollution, poor diet, or infection—and a new project aims to build the first epigenetic ageing clocks for birds to measure exactly how the environment drives biological ageing. Most ageing research relies on lab-bound fruit flies, fish, or rodents, which cannot capture the complex, real-world mix of stressors that wild vertebrates experience. Birds offer a solution: decades of detailed field studies have already collected tissue samples and life-history data from species exposed to urbanisation, climate shifts, and industrial contaminants. Yet no epigenetic clock exists for any common bird model. This project fills that gap by developing clocks for three bird species and a pan-avian clock spanning many more. If successful, these tools will let researchers pinpoint which environmental factors accelerate ageing—and which protect against it. The work is fundamental science: it probes how early development resets the ageing clock, a phenomenon first hinted at when Dolly the sheep was cloned from an aged cell. Deeper understanding of these mechanisms could eventually inform human health strategies, but the immediate payoff is a new lens on ageing across vertebrates, with applications in ecology, conservation, and agriculture.
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Worldwide, the proportion of older people in human populations is growing rapidly: based on WHO estimates, between 2015 and 2050 the proportion of the global population over 60 will double. As age is the predominant risk factor for the majority of pathologies, this growth will be accompanied by widespread health challenges. I propose to widen the availability of tools to identify general drivers of enhanced risk - across vertebrates - by considering organisms and contexts that have previously been overlooked. I will achieve this by developing epigenetic ageing clocks for birds and leveraging on the numerous detailed long-term studies, from which biological samples and metadata are available, on the impact of environmental factors such as diet, infection, climate, urbanisation and industrial pollution. Epigenetic clocks have revolutionised the fields of ageing and gerontology, and have opened new research avenues such as the area of epigenetic rejuvenation. These tools enable the measurement of biological ageing - the rate of physiological and molecular ageing of a tissue or a whole organism, by accurately quantifying age-related changes of chemical marks on DNA. The ticking rate of such clocks is not constant, as methylation is highly sensitive to environmental and life-style factors - infection, dietary factors, physical activity, reproductive measures and lifestyle stresses can cause age acceleration or deceleration. Yet there remains much to be learned about how the broad or direct environment affects the rates of ageing. Classical ageing research models such as the fruit fly, fish and rodents, pose limitations to the study of external environmental factors in the natural environment, as they are usually studied in a single context (the lab) and the results are not always translated to other vertebrates or contexts. Expanding methylation studies to other vertebrate systems will allow us to identify a much greater range of intersecting environments and stressors that impact ageing. It has also been recently shown that mammals undergo an age reset very early in their embryonic development, which is likely a universal phenomenon, speculated upon since the development of Dolly the Sheep from aged cells. How the environment affects this reset is not yet studied, and mammals represent a challenging system to do so. Birds are a long-standing early development model system that can overcome these challenges. Epigenetic clocks, however, are not yet developed for any common bird model. I propose to make epigenetic clocks for avian research to study the environmental effects on ageing, both during pre-natal development and adulthood. My objectives are: to develop and benchmark epigenetic clocks for three common bird model species where experimental or environmental data is available to probe for drivers of accelerated age develop a pan-avian clock through further data harvesting for a diverse range of species as a general tool with broader use This work will generate new knowledge to progress our understanding of the rules of life and the fundamental biological mechanisms responsible for early developmental age reset, age-related degenerative processes and the environmental factors that affect them. Epigenetic clocks will be also applicable in the context of infection, evolutionary biology, bird ecology, conservation, and agriculture. Given our ageing population, this knowledge is critical to progressing world-leading research that can be applied to wider societal and environmental benefit. The benefits of avian epigenetic clocks are thus far-reaching and extend beyond fundamental biology and ageing.
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