Heritability of the rate of ageing: novel statistics and models to quantify ageing

点击翻译按钮获取中文摘要

Why and how do organisms age and ultimately die? This is one of the big unsolved questions in biology, and when humans are concerned the Holy Grail of medical science. Traditionally ageing has been studied within the realm of physiology and medicine; senescence has been incorporated into ecology and evolution due to compelling evidence of ageing in wild populations of birds and mammals. Also, in the wild, physiological performance reduces with age (reproduction and parental care reduce), telomeres shorten (a biomarker of aging) and survival decreases with age. For us to now understand the evolution of ageing and its underlying physiological mechanisms we must separate environmental effect and genetic effects on the ageing process. In addition, demographic analysis of mortality can partition the underlying physiological mechanisms using statistics. Demography of death records is as close to the biology of actual death as possible and reveals two main components: the increasing risk of death with age - ageing rate - and frailty - the vulnerability to death from ageing-related causes. This proposal seeks to develop a novel statistical approach to estimate environmental and genetic effects in these two demographic properties. Our group also studies the ideal population to subsequently test for environmental and genetic effects on ageing rate and frailty: the house sparrow population on Lundy island which we have monitored for over 14 years and for which we have worked out the complete pedigree (who-is-related to whom) using DNA fingerprinting. In addition we aim to test the first theoretical model we developed of environmental effects on frailty, irreconcilable with current theoretical models of ageing to further increase our understanding of the mechanisms that cause ageing and how we could slow it down. This is possible thanks to the pioneering work of our proposed international partner, Prof Marc Tatar (Brown University, USA). Tatar conducted the first and only studies that have estimated the heritability of ageing rate and frailty (both in insects), has pioneered the statistics to disentangle these factors, and his lab has the unique skills and tools in place to assess the detailed demography needed to test the proposed theoretical model of frailty.