July 23, 2013 The final biological events in the life of a worm are described in a new article, published July 23 in the open access journal PLOS Biology. The paper reveals how death spreads like a wave from cell to cell until the whole organism is deceased.
The deaths of individual cells trigger a chemical chain reaction leading to the breakdown of cell components and a build-up of molecular debris. The molecular mechanisms of this process are reasonably well understood at a cellular level, but far less is known about how death spreads throughout an organism at the end of its life.
In worms, the spread of death can easily be seen under a microscope as a wave of blue fluorescence travelling through the gut of the worm. The new study, led by Professor David Gems from the Institute of Healthy Ageing at UCL, reveals that this fluorescence is caused by a cell death pathway called necrosis, and its spread throughout the organism is dependent on calcium signalling.
"We've identified the chemical pathways of self-destruction that propagate cell death in worms, which we see as this glowing blue fluorescence travelling through the body," explained Professor Gems. "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 active in mammals, confirming the worm can provide a useful model for understanding cell death, and how to prevent it, in other animals.
The study also links the mechanisms of cell death to the appearance of the blue fluorescence. The source of this fluorescence was previously thought to be a substance called lipofuscin, which emits light of a similar colour. Lipofuscin has previously been linked to ageing, since it accumulates with increasing molecular damage. However, the new findings implicate another molecule called anthranilic acid as the source of the blue hue and show that lipofuscin is not actually 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.
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- Cassandra Coburn, Erik Allman, Parag Mahanti, Alexandre Benedetto, Filipe Cabreiro, Zachary Pincus, Filip Matthijssens, Caroline Araiz, Abraham Mandel, Manolis Vlachos, Sally-Anne Edwards, Grahame Fischer, Alexander Davidson, Rosina E. Pryor, Ailsa Stevens, Frank J. Slack, Nektarios Tavernarakis, Bart P. Braeckman, Frank C. Schroeder, Keith Nehrke, David Gems. Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans. PLoS Biology, 2013; 11 (7): e1001613 DOI: 10.1371/journal.pbio.1001613
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