OPTiAGE · The trade-off between longevity and reproduction: optimal control of aging
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-09-01 → 2020-08-31
- EU contribution
- €187,420
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
The trade-off between longevity and reproduction: optimal control of aging
Problem being addressed: Animals adjust their rate of aging depending on nutritional conditions. In particular, almost all animals live longer under moderate dietary restriction. The goal of this project was to understand why most animals show this behaviour and understand the underlying molecular mechanisms. We aimed at testing the hypothesis that animals change the allocation of their resources between repair and growth /reproduction. Importance for society: Over the past decade, numerous companies have aimed at developing drugs or dietary treatments that can extend the lifespan of humans. To safely apply such drugs that interfere with the natural molecular regulation that controls the rate of aging, it is important to understand the endogenous, evolutionarily selected function of this regulation. To this end we have established experimental tools using the nematode C. elegans as a model system to address these questions using a quantitative approach that allows for evoutionary modelling and comparison between data and experiments. The overall objective: (i) to experimentally test whether the limitation of resources imposes a trade-off between longevity and reproduction that defines an optimal investment in self-maintenance maximizing fitness (ii) to ask if animals adjust their relative investment in self-maintenance to maximize their fitness in response to environmental change.
Data: CORDIS, © European Union
Project objective
The lifespan of genetically identical organisms varies depending on the environment they are exposed to. A well-known example is the extension of lifespan by nutrient restriction, as observed in animals as diverse as nematodes and rhesus monkeys. Why does the lifespan of animals change with environmental conditions? Is there an advantage to living longer when food is poor, and to living shorter when food is plentiful?Evolutionary theory, known as the disposable soma theory (DST), proposes that organisms age due to the accumulation of damage. According to theory, aging can be delayed by continuous damage repair, but such repair requires resources which are then unavailable for other tasks, such as reproduction. The DST therefore postulates a trade-off between longevity and reproduction dictated by the limitation of available resources. The optimal allocation of resources to self-maintenance depends on the environment. In particular, increased allocation to self-maintenance is predicted to maximize fitness when nutrients are scarce.Combining theory and experiment, I will investigate how the optimal allocation of resources to self-maintenance depends on nutrient availability using the nematode C. elegans as a model system. I will quantify the partitioning of resources between self-maintenance and reproduction using isotope labelling and kinetic modelling, and modulate resource allocation using available genetic alleles and directed mutation. Employing a competitive growth assay, I will test if fitness depends on resource allocation by an inverse U-shaped function, as predicted by theory and examine how the optimal resource allocation depends on nutrient availability. I will thereby assess if worms adapt their rate of aging to maximize their fitness in different environments.Ultimately, the proposed combination of mathematical modelling and developmental genetics will pave the way for a new line of research using optimality principles to study organismal development.
Original text from CORDIS.
Participants
- FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION · BASELCoordinatorSwitzerland
Links
Data: CORDIS, © European Union