To keep muscles strong, the 'garbage' has to go

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To keep muscles strong, the 'garbage' has to go

http://www.eurekalert.org/pub_releases/2009-12/cp-tkm112309.php

In order to maintain muscle strength with age, cells must rid themselves of the

garbage that accumulates in them over time, just as it does in any household,

according to a new study in the December issue of Cell Metabolism, a Cell Press

journal. In the case of cells, that waste material includes spent organelles,

toxic clumps of proteins, and pathogens.

The researchers made their discovery by studying mice that were deficient for a

gene required for the tightly controlled process of degradation and recycling

within cells known as autophagy. Those animals showed profound muscle atrophy

and muscle weakening that worsened with age.

" If there is a failure of the system to remove what is damaged, and that

persists, the muscle fiber isn't happy, " said Marco Sandri of the University of

Padova in Italy. Damaged and misfolded proteins pile up along with dysfunctional

mitochondria, distended endoplasmic reticulum, free radicals, and other aberrant

structures. Eventually, some of those muscle cells die, and " the muscles become

weaker and weaker with age. "

The muscle wasting observed in the mice seems to bear some resemblance to

certain forms of muscle-wasting diseases, Sandri said. He now suspects that this

kind of mechanism may offer insight into some of those still-unexplained

conditions, as well as the muscle weakening that comes with normal aging (a

condition known as sarcopenia).

Researchers knew before that excessive autophagy could also lead to muscle loss

and disease. The new findings highlight the importance of maintaining a normal

level of autophagy to clear away the debris and keep muscles working properly.

Although the discovery seems to make perfect sense in retrospect, it wasn't what

Sandri's team had initially anticipated.

" We thought if you reduced autophagy it might protect against atrophy, " he said.

" Instead, it's the opposite. We realized, OK, of course, if you don't remove the

damage, it triggers weakness. "

The findings may have clinical implications, he says. There has been interest in

developing therapies to block proteins' degradation for treating certain

muscle-wasting disorders. But in some cases, at least, " it may be better to

activate autophagy and remove the garbage in the cells, " Sandri said. The

researchers think similar treatments might combat aging sarcopenia as well,

noting that another study has shown a decline in the efficiency of autophagy

during aging.

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The researchers include Eva Masiero, Dulbecco Telethon Institute, Padova, Italy,

Venetian Institute of Molecular Medicine, Padova, Italy, University of Padova,

Padova, Italy; Agatea, Venetian Institute of Molecular Medicine, Padova,

Italy; Cristina Mammucari, University of Padova, Padova, Italy; Bert Blaauw,

Venetian Institute of Molecular Medicine, Padova, Italy, University of Padova,

Padova, Italy; Emanuele Loro, Venetian Institute of Molecular Medicine, Padova,

Italy; Masaaki Komatsu, Tokyo Metropolitan Institute of Medical Science, Tokyo,

Japan; Metzger, Centre National de la Recherche Scientifique, INSERM,

Illkirch-Cedex, France; Carlo Reggiani, University of Padova, Padova, Italy;

Stefano Schiaffino, University of Padova, Padova, Italy; and Marco Sandri,

Dulbecco Telethon Institute, Padova, Italy, Venetian Institute of Molecular

Medicine, Padova, Italy, University of Padova, Padova, Italy.