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

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.

Ageing research has the potential of high societal impact in term of potential drugs to slow ageing down. It is not our aim to contribute to the development of such drugs but any increase in the insights into the fundamental workings of ageing physiology will bring us closer to such interventions, for example mimicking the remarkable increases in healthy lifespan that can be obtained via dietary restriction. More directly, the proposal will contribute to two main areas of impact, human demography and conservation.

Human Demography
All current political decisions on economy, health care and demography are based on projections from current models of life expectancy and birth rates. The ageing population brings large economical challenges because a smaller proportion is paying (income) taxes, because of the lower birth rate compared to 30-60 years ago. This increasing proportion of elderly also need adequate pensions and health care that have to be provided by a smaller proportion of young individuals. It is thus crucial to predict demographic changes and life expectancy properly. Understanding heritability of ageing rate compared to frailty will also be applicable to human populations. We know now that human populations differ mainly in frailty, but whether this is purely environmental variation or also genetic, and how variable the genetic effects and/or environmental effects on ageing rate are, remains a black box. The development of the proposed statistics will allow the opening of this black box to more adequately predict the future of human longevity and demography and adjust political decision making accordingly. We will disseminate our findings to demographers using the Current Research in Evolutionary Demography mailing list of the Evolutionary Demography society (Dr Simons is a member). We also hold contacts with mathematician Dr Avraam Demetris (University of Liverpool) who will be happy to introduce our findings to his contacts with demographers in government and pension funds.

Conservation
Understanding ageing biology and especially variation in its genetic and environmental components can help conservation efforts and improve the management of zoo and wild populations. Predicting the turnover in adults in a population, depending on environmental and genetic effects on frailty versus ageing rate, will yield a more precise and balanced picture of the sustainability of a population. By estimating especially the genetic component it also models the expected demography in generations to come.
In our funded NERC grant J024597/1, which focuses on trans-generational effects of senescence and telomeres, we received support for our aim to reach out to zoos and conservation agencies with our findings, so that these beneficiaries can adjust their breeding and management policies accordingly. Our current proposed research has the same merits and will thus also be relevant to these two beneficiaries, and we will include our findings in our outreach accordingly.
Public outreach
As also outlined in our pathways to impact statement of the funded NERC grant J024597/1 we are actively engaging the public in our research using the following tools. We are establishing a blog http://lundysparrows.blogspot.co.uk/. We are committed to open access and supply lay summaries with our papers. Moreover, we actively engage with the Lundy Field Society and the British Trust for Ornithology (BTO) about our finding in the Lundy sparrow population. During fieldwork we actively engage with the many tourists visiting the island and take the time to explain what we are doing and what we achieve by colour banding and monitoring all house sparrows on the island.