Anti-Aging
| Researchers working on aging have found how death spreads in C. Elegans like a wave from cell to cell until the whole organism is deceased. The spread of death can easily be seen under a microscope as a wave of blue fluorescence travelling through the gut of the worm. |
In the final hours of a nematode worm’s life, a wave of cell death propagates along the length of its body. But, as if to have one last hurrah, the dying cells put on a bright blue light show, according to a paper published online in PLOS Biology.
The discovery of this peculiar death-related phenomenon came as a result of studies into aging, said University College London’s David Gems. One of the prevailing theories to explain aging in organisms, he said, is that throughout life there is a slow accumulation of damage to cellular components. In mammals, some of that damaged material accumulates in the lysosomes of aging cells as a substance called lipofuscin—“a sort of biological crap,” Gems said.
Gems studies aging in the nematode worm C. elegans, and like his fellow worm researchers, he assumed these tiny creatures also accumulated lipofuscin as they aged. Although lipofuscin had never been isolated from C elegans, the assumption was based on the fact that worms develop a fluorescent emission as they age, which fits with the fact that lipofuscin itself emits fluorescence. “Worm biologists said, ooh it looks like lipofuscin, and it became almost taken as a fact,” Gems said.
But Gems became suspicious. For one thing, although lipofuscin in a test tube has the same emission wavelength as the fluorescence produced by C. elegans, its wavelength in mammalian cells is different. And the fluorescence seen in the worms primarily builds up in slightly different organelles—lysosome-like gut granules.
“What people had done is look at populations of worms,” he said, which glow brighter as the group ages. “But what we found when we looked at individual worms is that there is no increase in fluorescence until they die.”
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Analyzing the contents of isolated gut granules from the worms’ intestinal cells revealed the true source of blue fluorescence: a substance called anthranilate. The team found that while the fluorescence of anthranilate was quenched by the acidity within its gut granule home, when the organelles’ membranes deteriorated upon cell death, or necrosis, anthanilate was released into the more alkaline cytoplasm, activating its fluorescence. Inhibiting pathways involved in necrosis prevented the death-related burst of fluorescence.
The fluorescence essentially acts as a marker of necrosis, said Gems. Indeed the wave of head-to-tail fluorescence reflected a wave of necrosis through the dying worm. It is not clear why the wave of necrosis always initiates at the head, but it does so even if the insult that triggers death—for example, intense heat—is applied to the posterior end of the worm. “It’s a total mystery,” Gems said.
Such propagating waves of necrosis are also seen, albeit locally, within damaged tissues in humans, such as during a heart attack or stroke. Thus dying worms might provide more than a pretty light show. For studying how necrosis spreads from cell to cell in human disease, and how to limit that spread, “this is going to be a fantastic model,” said Curran.
Annalee Newitz at Io9 writes, "Humans may not glow blue as we die, but our cells do send out chemical signals like those we can see in worms. Perhaps one day we'll be able to untangle the chemical pathway to death, and prevent that chilling necrotic cascade from overtaking our bodies before we are ready to die."
SOURCE The Scientist
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