What can worms tell us about human ageing?
Worms can tell us more about human ageing than you might think, according to research led by the Babraham Institute. In a cluster of papers, the latest of which has just been published, shows how researchers have used the tiny worm C. elegans to understand more about the link between metabolism and ageing.
C. elegans is one of the best model organisms to investigate the process of ageing because of its short lifespan of around 2-3 weeks. It also shares many of its core metabolic pathways with humans and many of the key genetic players in determining the lifespan of worms have been found to do the same in humans.
“One major barrier for fully exploiting the potential of C. elegans as a research tool was the lack of a model uniting everything that was known about C. elegans metabolism,” says Janna Hastings, a PhD student in the Casanueva lab at the Babraham Institute. “To overcome this, we initiated a global team effort to reconcile existing and conflicting information on metabolic pathways in C. elegans into a single community-agreed model and launched the resulting WormJam resource in 2017.”
The Casanueva lab at the Babraham Institute use C. elegans to understand how metabolism changes during the normal course of ageing and how a variety of interventions that change metabolic fluxes can extend the length and quality of life. Physical changes evident in ageing worms point towards the loss of central metabolic capabilities as the worms age. The developed metabolic model was valuable to their research but had one key limitation; it best reflected what was happening during the growing phase of C.elegans, not the ageing phase.
“One of the key challenges that we face when studying ageing is that the modelling tools available are optimised for animals or cells that are in the process of growing, which is not happening in aged animals,” explains Dr Olivia Casanueva, group leader in the Epigenetics programme at the Babraham Institute.
Confronted with this challenge, the researchers re-optimised the modelling tool and were able to adapt the tool to study metabolic fluxes during ageing.
So, what can worms tell us about human ageing? A lot more now, thanks to the WormJam model and the subsequent development to adapt this for ageing studies.
“This re-optimisation of the model for ageing animals represents a significant technical advance for the field and will allow more accurate predictions of metabolic fluxes during the course of ageing,” concludes Dr Casanueva. “By developing our understanding of the experimental model of ageing, we can gain valuable insight into what’s happening in humans – taking a step towards achieving healthier ageing.”
Notes to editors
This work was supported by funding from the ERC, BBSRC and MRC and the Rutherford Foundation Fellowship to Abraham Mains. The WormJam community project was funded by the GENiE COST action action and received support from the Babraham Institute's BBSRC Knowledge Exchange and Commercialisation grant.
Research paper: Hastings et al. frontiers in Molecular Biosciences: Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During C. elegans Aging Multi-omics and genome-scale modeling reveal a metabolic shift during C. elegans aging. Frontiers in Molecular Biosciences. DOI: 10.3389/fmolb
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