Details of Award
NERC Reference : NE/W001020/1
Testing classical and emerging evolutionary theories of ageing in ecologically relevant environments
Grant Award
- Principal Investigator:
- Professor A Maklakov, University of East Anglia, Biological Sciences
- Co-Investigator:
- Professor T Chapman, University of East Anglia, Biological Sciences
- Grant held at:
- University of East Anglia, Biological Sciences
- Science Area:
- Terrestrial
- Overall Classification:
- Panel C
- ENRIs:
- Biodiversity
- Environmental Risks and Hazards
- Science Topics:
- Animal & human physiology
- Ageing
- Population Ecology
- Abstract:
- Ageing, a physiological deterioration of an organism with advancing age, results in reduced reproductive performance and/or increased likelihood of death. Ageing reduces fitness and plays a pivotal role in population dynamics, but our understanding of the biology of ageing is still incomplete. Evolutionary theory of ageing posits that ageing evolves because the strength of selection on traits decline with age. However, this theory does not explain which physiological processes cause senescence. The most dominant physiological theory of ageing is the Disposable Soma Theory (DST) which maintains that competitive energy allocation between growth, reproduction and longevity results in imperfect somatic maintenance and repair, so that ageing is caused by slow accumulation of unrepaired cellular damage. The DST has been increasingly challenged by studies showing that increased longevity does not necessarily result in reduced fitness thereby questioning the centrality of the energy trade-off between growth, reproduction and longevity in the evolution of ageing. The emerging new theory, the Developmental Theory of Ageing (DTA), argues that ageing is caused by biological processes that are optimised for development, growth and early-life reproduction and become harmful with advancing age because natural selection acting on age-specific gene expression is too weak to optimise it. Specifically, evolutionarily conserved nutrient-sensing molecular signalling pathways are predicted to play a fundamental role in ageing because these "life-history nexus" pathways regulate the response of the organisms to environmental change. Crucially, these two theories of ageing provide distinct and unique predictions regarding the effect of the experimental lifespan extension on other key life-history traits and, ultimately, on Darwinian fitness. The DST predicts the fitness cost of increased longevity through negative effects on either development, growth or reproduction. The DTA predicts that optimisation of gene expression in adulthood can improve the organismal physiology and concurrently increase longevity and fitness. This is because the DTA considers ageing to be a result of insufficient selection on late-life gene expression rather than insufficient resources for somatic maintenance and repair. The predictions of these two theories have never been tested experimentally against each other in complex ecologically relevant environments. Recent work from our laboratory provides the proof-of-principle for the idea that adulthood-only IIS downregulation using feeding RNA interference (RNAi) approach to knockdown daf-2, the "grim reaper gene" that encodes an insulin receptor-like protein in Caenorhabditis elegans nematodes can improve longevity and fitness in simple and benign laboratory environment. Here we propose a novel approach that builds on our previous work to combine the genetic "tools" available for C. elegans with fitness assays in complex ecologically relevant environments. We will first test whether daf-2 RNAi nematodes outperform the control worms under a broad range of ecologically relevant stressful environments across three generations. We then will test whether daf-2 RNAi animals will perform better in complex controlled microcosms that will mimic their natural environments. Finally, we will perform the first-of-a-kind experiment where we will test whether IIS downregulation in adult worms improves population growth and viability in nature. This three-pronged research program will bridge the knowledge gap by providing the very first set of experiments that will allow us to test whether ageing and fitness can be concurrently improved in natural environments. By combining ecological relevance and complexity with the immense power of C. elegans model system for genetic and epigenetic research in a unique and unprecedented way, this project will provide a step-change in our understanding of how ageing evolves.
- NERC Reference:
- NE/W001020/1
- Grant Stage:
- Awaiting Event/Action
- Scheme:
- Standard Grant FEC
- Grant Status:
- Active
- Programme:
- Standard Grant - NI
This grant award has a total value of £522,850
FDAB - Financial Details (Award breakdown by headings)
| DI - Other Costs | Indirect - Indirect Costs | DA - Investigators | DA - Estate Costs | DI - Equipment | DI - Staff | DI - T&S | DA - Other Directly Allocated |
|---|---|---|---|---|---|---|---|
| £63,173 | £170,696 | £29,521 | £36,103 | £15,747 | £197,605 | £7,723 | £2,284 |
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