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C. elegans study sparks hope for slowing muscle decline caused by ageing

muscle decline mitochondria dysfunction muscle atrophy calcium buildup collagen degradation

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#1 Engadin

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Posted 08 June 2019 - 01:57 PM


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Muscle decline caused by ageing and certain diseases could be dramatically slowed by stopping a chain reaction that damages cells, new research shows.

 

The study revealed the previously unknown steps by which dysfunction of mitochondria—the so-called "powerhouses" of cells—harms muscle health and leads to atrophy (wasting away).

 

The research team, from the universities of Exeter and Nottingham (UK) and Tohoku University in Japan, showed that inhibiting various stages of this process suppressed muscle atrophy.

 

The research was carried out on a species of worm called Caenorhabditis elegans—recently used in a muscle study on the International Space Station because their muscle cells resemble those of humans.

 

"Mitochondrial dysfunction is a key feature of several muscle diseases, but treatments are currently limited," said Dr. Timothy Etheridge, of the University of Exeter.

 

"Our research shows that mitochondrial dysfunction causes calcium to build up in cells, which in turn activates enzymes that degrade collagen.

 

"Collagen is vital for giving structure to the outside of cells, so degradation of collagen destabilises muscle.

 

"In this study, we used experimental drugs to inhibit the enzymes that degrade collagen—and the results show this suppressed muscle decline caused by dysfunctional mitochondria.

 

"We found the same effect in worms used to model Duchenne muscular dystrophy, which causes severe muscle weakness."

 

More research is needed, but the findings raise the prospect of new therapies to delay muscle atrophy caused by ageing and conditions such as Duchenne muscular dystrophy.

 

 

S O U R C E :   MedicalXpress



#2 Phoebus

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Posted 08 June 2019 - 02:27 PM

 

 

Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans
 
Published Online:4 Jun 2019https://doi.org/10.1096/fj.201802298R
Abstract

Mitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)–based proteolysis and, consequentially, muscle cell dystrophy. We found that inhibition of the mitochondrial electron transport chain causes paralysis as well as muscle structural damage in the nematode Caenorhabditis elegans. This was associated with a significant decline in collagen content. Both paralysis and muscle damage could be rescued with collagen IV overexpression, matrix metalloproteinase (MMP), and Furin inhibitors in Antimycin A–treated animal as well as in the C. elegans Duchenne muscular dystrophy model. Additionally, muscle cytosolic calcium increased in the Antimycin A–treated worms, and its down-regulation rescued the muscle damage, suggesting that calcium overload acts as one of the early triggers and activates Furin and MMPs for collagen degradation. In conclusion, we have established ECM degradation as an important pathway of muscle damage.—Sudevan, S., Takiura, M., Kubota, Y., Higashitani, N., Cooke, M., Ellwood, R. A., Etheridge, T., Szewczyk, N. J., Higashitani, A. Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans.

 

 

 

so it seems they wanted to overexpress CIV...by what means did that happen? 

 

also wanted to  suppress MMP and furin 

 

but they don't mention HOW exactly they did any of that. Anyone have the full study?

 

 

 


Edited by Phoebus, 08 June 2019 - 02:35 PM.


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Also tagged with one or more of these keywords: muscle decline, mitochondria dysfunction, muscle atrophy, calcium buildup, collagen degradation

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