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Laser Ablation of Lipofuscin

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#211 seivtcho

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Posted 29 October 2011 - 04:19 PM

Then the idea for ablating lipofuscin with a laser becomes more impossible.

What are the brown - yellowish granules then?

#212 AgeVivo

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Posted 29 October 2011 - 10:12 PM

and are they unhealthy for the worms?
"lipofuscin" was described as the culprit to eliminate, but what was hoped in this project was to destroy "bad aggregates" in the worms, without killing the worms.

#213 s123

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Posted 30 October 2011 - 02:26 PM

Under UV light, blue fluorescence is visible in the intestinal cells of C. elegans. Mean levels of this fluorescence increase in aging worm cohorts(1). It has been suggested that the fluorescent substance is lipofuscin, a complex aggregate of oxidised proteins and lipids. Lipofuscin occurs in aging mammalian cells and has similar spectral properties(2). Blue fluorescence is thus often used as a biomarker of aging in C. elegans. When we monitored individual worms (rather than cohorts) as they aged, we saw no increase in fluorescence. Instead, as the worms died, we saw a rapid and striking increase in fluorescence (~5 fold, p = 2.8e-13\; time lapse photography). This fluorescence was propagated in a wave along each worm as it died. A similar increase was also seen in young adult worms when we killed them. Hyperoxia caused increased protein oxidation but did not affect levels of blue fluorescence. Altogether, our findings strongly imply that the blue fluorescent material is not lipofuscin or any kind of biomarker of aging, but rather an indicator of death. We then asked how such death fluorescence is generated. In the necrotic calpain-cathepsin protease pathway of mammals(3) and nematodes(4), lysosomal lysis causes cytosolic acidosis, which leads to cell death via peptidase activation. We employed necrosis pathway mutants to block the pathway, and tested effects on death fluorescence. Knockdown of intracellular calcium release (crt-1, unc-68), or cysteine (tra-3) or aspartyl (cad-1) proteases, or inhibition of lysosomal acidification (vha-12) all significantly decreased death fluorescence levels. Moreover, cytosolic acidosis immediately precedes death fluorescence. This suggests that death fluorescence is a terminal product of the necrotic cell death pathway. The fluorescent material, which is non-proteinaceous, can be purified using HPLC. Mass spectrometry identifies a single molecular species, which we are now analyzing. Our work implies that the blue fluorescent substance in the worm intestine is not lipofuscin but, instead, a terminal product of necrotic death. Moreover, it suggests that intestinal necrosis, and its propagation along the worm, plays a major role in C. elegans organismal death. (1) Gerstbrein, Aging Cell, 2005 (2) Klass, Mech Ageing Dev, 1977 (3) Yamashima, Cell Calcium, 2004 (4) Xu, Neuron, 2001.


http://www.wormbase....921;class=Paper

#214 Mind

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Posted 30 October 2011 - 03:27 PM

But does this mean that there is NO lipofuscin in c.elegans cells (unlikely) and that a well-tuned laser frequency would not be able to destroy lipofuscin?

#215 seivtcho

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Posted 02 November 2011 - 09:19 PM

By the way, what is the chemical composition of the lipofuscin?
Does anyone can provide a chemical formula for the lipofuscin?





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