The final biological events in the life of a worm are described today, revealing how death spreads like a wave from cell to cell until the whole organism is dead.
When individual cells die, it triggers a chemical chain reaction that leads to the breakdown of cell components and a build-up of molecular debris. The molecular mechanisms of this are reasonably well understood at a cellular level, but we know much less about how death spreads throughout an organism at the end of its life.
In worms, the spread of death can be seen easily under a microscope as a wave of blue fluorescence travelling through the gut of the worm. The study, led by researchers funded by the Wellcome Trust and BBSRC, reveals that this fluorescence is caused by a cell death pathway called necrosis and its spread throughout the organism is dependent on calcium signalling.
Professor David Gems from the Institute of Healthy Ageing at UCL (University College London), who led the study, explains: "We've identified a chemical pathway of self-destruction that propagates cell death in worms, which we see as this glowing blue fluorescence travelling through the body. It's like a blue grim reaper, tracking death as it spreads throughout the organism until all life is extinguished.
"We found that when we blocked this pathway, we could delay death induced by a stress such as infection, but we couldn't slow death from old age. This suggests that ageing causes death by a number of processes acting in parallel."
The mechanisms involved are similar to those that are active in mammals, confirming that the worm can provide a useful model to understand cell death in people.
The study, published online today in 'PLoS Biology', also links the mechanisms of cell death to the appearance of the blue fluorescence. The source of the blue fluorescence was previously thought to be a substance called lipofuscin, which emits light of a similar colour and has been linked to ageing because it accumulates with increasing molecular damage. However, the new findings implicate another molecule called anthranilic acid as the source and show that lipofuscin is not involved.
"Together the findings cast doubt on the theory that ageing is simply a consequence of an accumulation of molecular damage. We need to focus on the biological events that occur during ageing and death to properly understand how we might be able to interrupt these processes," added Professor Gems.
Notes to editors
Reference: Coburn C et al. Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans. Plos Biology 2013.
Video and images
Images are available on request from firstname.lastname@example.org.
The short video (above) about the work of Professor Gems' lab into the biology of ageing in C. elegans is available to embed from the Wellcome Trust YouTube channel. This includes footage of the blue fluorescent wave as the worm dies.
About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. For more information visit: Wellcome Trust .
About UCL (University College London)
Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender and the first to provide systematic teaching of law, architecture and medicine. We are among the world's top universities, as reflected by our performance in a range of international rankings and tables. According to the Thomson Scientific Citation Index, UCL is the second most highly cited European university and the 15th most highly cited in the world. UCL has nearly 27,000 students from 150 countries and more than 9,000 employees, of whom one third are from outside the UK. The university is based in Bloomsbury in the heart of London, but also has two international campuses - UCL Australia and UCL Qatar. Our annual income is more than £800 million. For more information visit: www.ucl.ac.uk .
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by Government, and with an annual budget of around £467M (2012-2013), we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.