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A worm wide web: scientists create network of age-related genes

Key points:

• A large-scale analysis by researchers from the Casanueva lab predicts key genes for longevity in a long-lived nematode worm used as a model organism.
• They found that the longevity network could be represented by an hourglass shape, with a core of key genes that receive input from an upper layer whilst providing output to a bottom layer.
• This strategy allowed researchers to discover 50 new ageing genes, 43 of them with human equivalents.  

Ageing is a highly complex process with thousands of genes influencing our health, which poses a challenge for researchers looking to explain and target the underlying processes that lead to declining health. Researchers from the ����������̳’s Epigenetics research programme have published a map of genetic interactions in C. elegans in iScience which can be used to identify new genes that influence lifespan and that have equivalent genes in humans.

Researchers use simple model organisms like the nematode worm C. elegans to gather information that can inform studies on human ageing because many genes are shared or have counterparts in other species. However, there are some conceptual and technical challenges that apply to the study of ageing in model organisms. Dr Casanueva, Group leader in the Epigenetics research programme explains: “The way researchers usually study gene function is by disrupting its function and observing what happens. The disruption of some genes causes worms to live a very long-life. In this way, researchers have found the so-called ‘longevity-pathways’. However, the complexity underlying ageing means that it is not enough to focus on individual genes. We need to study the overall organisation of longevity by generating a systems-wide view.”

In collaboration with the physicist Marta Sales Pardo at University of Rovira i Virgili, Dr Casanueva and her lab set out to cast a wider net when it comes to studying longevity genes. Together they created the largest network of gene regulatory interactions that are found in a long-lived type of C. elegans. In this network, the relationships between genes are represented by lines, and represented in different layers based on the flow of information between genes. The middle of the web represents the genes with the most influence, in this case, they receive complex input signals and de-code them, and connect to an output layer of genes. The researchers found that most key genes for longevity belong to transcription factors and metabolic genes.

After narrowing down the number of genes to the most important ‘core’ the team were able to run genetic screens in the lab which helped them to identify which genes had the largest influence on lifespan. Their results pinpointed 50 new genes linked to ageing in worms identified, 43 of which have human equivalents.

Dr Casanueva added: “Advances in medicine have meant that the global population is living for longer, but, we need to be able to prevent the financial burden and personal suffering of unhealthy ageing. We can only do that if we understand the complex nature of ageing. Our study shows the power of using model organisms to build a detailed picture of the genetic influences on longevity. We have shown the predictive power of our computational framework and therefore its potential to accelerate gene discovery in the question of ageing in C. elegans and potentially in humans.”

Notes to Editors

Publication reference

Suriyalaksh, M, et al. Gene Regulatory Network inference in long-lived C. elegans reveals modular properties that are predictive of novel ageing genes, ISCIENCE (2022), doi:

Press contact

Honor Pollard, Communications Officer, honor.pollard@babraham.ac.uk

Image description: Diagram of analysis of the large-scale organisation of the global network

Affiliated authors (in author order):

Manusnan Suriyalaksh, former PhD student, Casanueva lab

Celia Raimondi, former postdoc, Casanueva lab

Abraham Mains, former PhD student, Casanueva lab

Anne Segonds-Pichon, Biological Statistician

Sheikh Mukhtar, former research assistant, Casanueva lab

Sharlene Murdoch, former senior research assistant, Casanueva lab

Rebecca Aldunate, visiting scientist, Casanueva lab

Felix Krueger, Bioinformatician, Bioinformatics facility

Simon Andrews, Head of Bioinformatics facility

Olivia Casanueva, Epigenetics programme group leader

Research funding

This research was funded by the European Research Council and the Biotechnology and Biological Sciences Research Council (BBSRC).

Additional/related resources:

News 3^rd November 2021, A brain switch that helps worms keep their cool

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As a publicly funded research institute, the ����������̳ is committed to engagement and transparency in all aspects of its research. The research described here used nematode worms called Caenorhabditis elegans (shortened to C. elegans) which is used as a model organism by researchers to understand human development and disease. The use of C. elegans in research is one of the ways by which we aim to reduce the numbers of animals we use in research.

Please follow the link to find out more about ways we work to meet the 3Rs principles: reduction, refinement and replacement in our research and when using animals in research.

About the ����������̳

The ����������̳ undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. ����������̳ focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through Institute Strategic Programme Grants and an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.

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