The Blue Wave of Death
This is a really amazing bit of research into what happens to a dying worm. Researchers have discovered a burst of intense blue fluorescence, visible under UV light, that propagates through the worm in the form of a ‘wave’ in it’s final minutes of life. The original research paper is Open Access and published in the journal PLOS Biology
✤ Cell death in an organism typically takes two forms; controlled (apoptosis) or uncontrolled (necrotic). Recent research has shown that even necrotic cell death can be a regulated process with a certain degree of control. But what are the molecular mechanisms for this?
✤ The classical hallmarks of necrosis include initiation by calcium ions, disruption of the cellular ‘suicide bags’ (known as lysosomes, which are organelles found within cells that contain enzymes that can digest and kill the cell), and the activation of enzymes that digest proteins (known as proteases).
✤ In order to better understand what happens during necrosis at the molecular and cellular level, researchers studied this process in the worm Caenorhabditis elegans. In C. elegans, the intestine cells contain both lysosomes and gut granules, which are large lysosome-related organelles. Under UV light, these gut granules emit blue florescence. But what exactly causes this blue glow, and how and why does it happen?
✤ It appears that blue fluorescence levels in worms increase only as they approach death (both natural, due to ageing, and unnatural due to lethal injury or stress). By observing dying worms, researchers discovered that the level of fluorescence changes very little until immediately prior to death, upon which there is a whopping 400% increase, which coincides with cessation of movement, i.e. death. They named this process “Death Fluorescence”.
✤ The researchers then carried out NMR analysis to pin down the identity of this mystery blue fluorescent substance. They discovered that death fluorescence is chemically anthranilic acid glucosyl esters, derived from the amino acid tryptophan.
✤ Next the researchers investigated whether this death fluorescence was generated by necrosis. Necrosis requires the release of calcium ions from within the cell, which then goes on to activate a cascade of signaling. They showed that death fluorescence is indeed dependent on this necrotic death cascade. They also show that calcium ion signaling is required for and precedes the spread of death fluorescence. The take home message is that during death, a wave of calcium ions spread from the front to the back of the worm, driving a wave of necrosis that leads to death fluorescence.
✤ The researchers also showed that death fluorescence also occurred in related nematode species. Indeed, there are tantalizing clues reporting blue fluorescence accompanying cell death in liver cells and yeast! This indicates that this process and its mechanism might be common to many diverse forms of life.
✤ Studies into the upper limits of human longevity have shown that removal of a single major age-related disease (cancer or heart disease) would only cause a small increase in lifespan. This is because multiple pathological processes act in parallel to increase age-related mortality. The mechanisms reported here are similar to cellular necrosis in mammals; this work is therefore an excellent model to study this process in more detail in order to better understand our own processes of aging and cellular death.