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Life-long telomere dynamics, health and fitness in a long-lived mammal

Funder: UK Research and InnovationProject code: BB/L020769/1
Funded under: BBSRC Funder Contribution: 544,176 GBP

Life-long telomere dynamics, health and fitness in a long-lived mammal

Description

Life expectancies in the UK have increased rapidly over the last century. If this continues, recent studies have predicted that the majority of babies born since 2000 will live to 100. Our ageing population poses serious economic and medical problems, unless we can find ways of alleviating the process of physiological deterioration and many diseases that are associated with old age. Simple biological measures (or 'biomarkers') capable of illuminating the wider process of ageing and predicting the onset of common diseases of old age could provide important new understanding of the underlying causes of individual variation in ageing rates, as well as interventions to promote healthy ageing. Telomere length (TL) is an exciting candidate biomarker of ageing. Telomeres cap and protect our chromosomes and become shorter with each cell division. When telomeres become very short, cells stop functioning properly, with potentially negative consequences for wider bodily function. Accordingly, the process of telomere attrition is thought to play an important role in the way we age. In humans, telomeres are usually measured in white blood cells, because blood is relatively easy to obtain, and average TL of these cells declines with age. Excitingly, short TL in adulthood predicts various age-related diseases and reduced subsequent survival. However, age only explains a small part of the massive variation in TL among individuals, and we currently do not know why adult TL varies so much. Is it because of genetic or environmental effects on TL at birth, or is it down to differences in growth rates or experiences through early life and adulthood which affect the rate of telomere shortening? To answer this question we need blood samples and information over the entire lifetimes of individuals. This has not been possible in humans because we are so long lived. Furthermore, there are considerable differences in the telomere biology of short-lived and long-lived mammals, so laboratory mice may be poor models for humans. In this project, we will use a remarkably detailed long-term study of Soay sheep on St Kilda to tackle the question of how and why TL varies across the entire lifespan and what this means for the ageing process. It might seem odd to be using wild sheep on a remote island for such a purpose. In fact, the telomere biology of sheep and humans is similar, and the Soay sheep are one of the most closely monitored populations of mammals anywhere in the world. Since 1985, every sheep has been individually marked and followed closely across its lifetime, so we know how quickly they grew, when they bred, where they lived, when they died and we have detailed information on their genetics and the environmental conditions they experience. Importantly, we also regularly re-capture these animals and have collected blood samples repeatedly from around 3000 individuals all the way from birth to death. We will measure TL from archived blood samples to test whether differences in TL in late adulthood are mainly the result of differences in TL at birth or in telomere loss thereafter. We will also test how genes and environment during development influence TL and how natural selection acts on variation in TL. The uniquely detailed, life-long nature of our study will provide the first tests of the causes of individual variation in telomere attrition rates across the entire lifespan of a long-lived mammal. We will also extend the fieldwork on St Kilda to collect samples for more extensive telomere and immunological analyses. Laboratory studies show that a few very short telomeres are enough to compromise cell function, and in white blood cells this could compromise our immune system. Using newly-collected field data and blood samples, we will test both of these predictions outside of the lab for the first time, shedding new light on how changes in TL may influence our ability to fight disease, maintain health and survive in later adulthood.

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