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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - OPTiAGE (The trade-off between longevity and reproduction: optimal control of aging)

Teaser

Summary

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.

Work performed

We established an experimental system that employs cultivation of individual animals of C. elegans in arrayed micro chambers. Animals are then imaged at a time resolution of 10 minutes using a live imaging microscope. We optimized experimental procedures to allow for concurrent imaging of more than 200 individuals. Development of a dedicated image analysis pipeline enabled us to make precise measurements of growth, size, development, and gene expression (using GFP reporters) at unprecedented throughput and accuracy. Establishment of this system has been, and will continue to be, instrumental for achieving the objectives of the OPTiAGE project. At the same time, we obtained important results that go far beyond the initially planned objective.

Final results

Specific results obtained:
During the reporting period, we fully validated our live imaging approach and obtained valuable results on the interplay between resource allocation, growth, and body size. Specifically we report the following findings:
- Genetically identical individuals differ from each other in their growth rate even if growing in the same environment.
- Fast growing individuals have a faster development.
- We found that genetic mutants that affect the rate of growth of individuals do not proportionally affect the body size due to coupling of growth and development.
- Future work will evaluate the influence of environmental conditions on resource allocation, aging and fitness (WP3).

Exploitation: The results of the OPTiAGE project will be exploited by future research projects that will greatly profit from this new methodologies and insights. We provide proof-of-concept that the combination of quantitative experiments and mathematical models, as previously mostly applied to a cellular system, can be translated to an organismal scale to reach fundamental biological insight. We therefore provide a stepping stone for a fundamentally new approach to organismal biology. Having established a novel quantitative approach to study organismal process will enable innovative collaborations with researchers across Europe and beyond and thereby benefit Europe\'s overall competitiveness.