Evolution and genetics of senescence in the wild
Lead Research Organisation:
University of Sheffield
Department Name: Animal and Plant Sciences
Abstract
All organisms age and eventually die. However, we know very little about the physiology that causes ageing or how ageing has evolved in the first place. We propose to study in detail how mortality risk changes with age and what the genetic contribution is to this. We reason that by understanding the underlying genetics we can both directly test how ageing has evolved, using methods that study how DNA sequences have changed through evolutionary time, and can deduce the mechanisms of ageing. We can then subsequently use this knowledge to understand what happens in a natural setting. Using novel statistics that we will develop, we will test for a genetic signal of ageing in natural populations. We will then identify the genes responsible for ageing using a model system, the fruitfly, and subsequently study both how these genes have changed through evolutionary time and the role of these specific genes in ageing in natural populations. We have gathered a team of international partners with the skills required to make this interdisciplinary project a success. Our work will contribute to understanding the fundamental biology of how and why ageing evolved, and will help us to begin to understand the genetic and cellular processes that cause ageing, with obvious potential future applications in medicine.
Planned Impact
Benefits to society
While people live longer, they increasingly suffer from ageing-related illnesses. Ageing research has the potential of high societal impact in terms of treatments, including drugs, to slow ageing down. Moreover, most common life threatening diseases can be considered diseases of ageing. For example, the positive effect that dietary restriction in mice has on lifespan and associated disease is so large that, if it could be directly translated to humans, the gain in healthy lifespan would be larger than that achieved by eliminating stroke, diabetes, cancer and cardiac disease. The potential gain from studying ageing biology in an evolutionary context is, therefore, not only fundamentally interesting, but it also has potential in future medical applications. We strongly propose that studying ageing from an evolutionary perspective will reveal fundamental universal aspects of the ageing process that we can use to make currently unimaginable progress in these areas.
More directly the proposal will also 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 of the population 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 healthcare, which have to provided and financed by a decreasing proportion of young individuals. It is thus crucial to predict demographic changes and life expectancy properly.
Understanding heritability of ageing rate compared to frailty (Objective 1) and improving current estimation methods using Bayesian statistics (Objective 2) 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. Heritability statistics should shine some light into 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. We also maintain contacts with a mathematician working on Gompertz Law in humans, Avraam Demetris, and his supervisor Prof Joao Pedro Magalhaes (University of Liverpool), who will be happy to introduce our findings to demographers in government and in pension funds, with whom they have regular interactions.
Conservation
Understanding ageing biology, and especially the genetic and environmental components of ageing, can help conservation efforts and improve the management of zoo and wild populations. Predicting the turnover in adults in a population depends on the environmental and genetic effects on frailty, versus ageing rate and the potentially associated genetics, and will yield a more precise and balanced picture of the sustainability of a population.
While people live longer, they increasingly suffer from ageing-related illnesses. Ageing research has the potential of high societal impact in terms of treatments, including drugs, to slow ageing down. Moreover, most common life threatening diseases can be considered diseases of ageing. For example, the positive effect that dietary restriction in mice has on lifespan and associated disease is so large that, if it could be directly translated to humans, the gain in healthy lifespan would be larger than that achieved by eliminating stroke, diabetes, cancer and cardiac disease. The potential gain from studying ageing biology in an evolutionary context is, therefore, not only fundamentally interesting, but it also has potential in future medical applications. We strongly propose that studying ageing from an evolutionary perspective will reveal fundamental universal aspects of the ageing process that we can use to make currently unimaginable progress in these areas.
More directly the proposal will also 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 of the population 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 healthcare, which have to provided and financed by a decreasing proportion of young individuals. It is thus crucial to predict demographic changes and life expectancy properly.
Understanding heritability of ageing rate compared to frailty (Objective 1) and improving current estimation methods using Bayesian statistics (Objective 2) 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. Heritability statistics should shine some light into 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. We also maintain contacts with a mathematician working on Gompertz Law in humans, Avraam Demetris, and his supervisor Prof Joao Pedro Magalhaes (University of Liverpool), who will be happy to introduce our findings to demographers in government and in pension funds, with whom they have regular interactions.
Conservation
Understanding ageing biology, and especially the genetic and environmental components of ageing, can help conservation efforts and improve the management of zoo and wild populations. Predicting the turnover in adults in a population depends on the environmental and genetic effects on frailty, versus ageing rate and the potentially associated genetics, and will yield a more precise and balanced picture of the sustainability of a population.
Publications
Afanasyeva A
(2018)
Human long intrinsically disordered protein regions are frequent targets of positive selection.
in Genome research
Bockwoldt M
(2019)
Identification of evolutionary and kinetic drivers of NAD-dependent signaling.
in Proceedings of the National Academy of Sciences of the United States of America
Corcoran P
(2017)
Determinants of the Efficacy of Natural Selection on Coding and Noncoding Variability in Two Passerine Species.
in Genome biology and evolution
Garratt M
(2017)
Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort.
in The journals of gerontology. Series A, Biological sciences and medical sciences
Girndt A
(2018)
Male age is associated with extra-pair paternity, but not with extra-pair mating behaviour.
in Scientific reports
Gossmann T
(2018)
Evidence for Strong Fixation Bias at 4-fold Degenerate Sites Across Genes in the Great Tit Genome
in Frontiers in Ecology and Evolution
Gossmann T
(2019)
Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity
in Current Biology
Kappei D
(2017)
Phylointeractomics reconstructs functional evolution of protein binding.
in Nature communications
Karr TL
(2019)
The Old and the New: Discovery Proteomics Identifies Putative Novel Seminal Fluid Proteins in Drosophila.
in Molecular & cellular proteomics : MCP
Kinsella CM
(2019)
Programmed DNA elimination of germline development genes in songbirds.
in Nature communications
| Description | We find widely divergent demography of mortality within genetically divergent lab lines of fruit flies. We have also associated this with specific SNPs in these lines and are following this up currently also within an evolutionary genomics framework. We have tested Strehler's law across 100 different fly lines, showing a biological foundation of this statistical law. We have further collected data on the mortality demography of ~140 lines which show highly divergent demography of mortality that we will use in our Genome Wide Association Framework. We have employed population genetics measures of selection across our fly lines and are investigating this within published sets of transcriptome data and within our own experimental data to test evolutionary theories of ageing. We find highly divergent lifespans for males and females and this varies by genotype. We are interpreting this currently within the context of sexually antagonistic selection and ageing. Further output generated through this grant has been a result from active national and international collaboration only made possible by this pump priming plus funding. E.g. collaboration on the evolutionary origins of telomere erosion across different species of birds. |
| Exploitation Route | We have extended our Bayesian models that will be of use of others working on ageing and the heritability of mortality rate. We further included uncertainty of sampling rate, which has surprising effects on the reliability of our estimates. This has wider implications within Ecology and a manuscript is currently in preparation for this with collaborators from CEFAS (UK) and the University of Sydney and Edinburgh. Our experimental demographic data on fruit flies will be shared with the community through the Survcurv framework once data collection is completed. |
| Sectors | Other |
| Description | Our work has started a collaboration with Dr Michael Spence now at CEFAS on Bayesian models of demography of mortality. We have supervised a NERC funded placement student together and our collaboration has extended into Dr Spence's work at CEFAS. |
| Sector | Other |
| Description | EPFL Lausanne |
| Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
| Country | Switzerland |
| Sector | Public |
| PI Contribution | N/A |
| Collaborator Contribution | maintains and supplied the experimental fly lines we need for the experiments outlined in the graph |
| Impact | manuscript is in preparation |
| Start Year | 2015 |