New Insight Into Factors That Drive Muscle-Building Stem Cells

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New Insight Into Factors That Drive Muscle-Building Stem Cells

http://www.medicalnewstoday.com/articles/93375.php

A report in the January issue of Cell Metabolism, a publication of

Cell Press, provides new evidence explaining how stem cells known as

satellite cells contribute to building muscles up in response to

exercise. These findings could lead to treatments for reversing or

improving the muscle loss that occurs in diseases such as cancer and

AIDS as well as in the normal aging process, according to the

researchers.

The researchers showed that a transient and local rise in an

inflammatory signal, the cytokine known as interleukin-6 (IL-6), is

essential for the growth of muscle fibers. The findings offer the

first clear mechanism for the stem cells' incorporation into muscle

and the first evidence linking a cytokine to this process, said Pura

Muñoz-Cánoves of Universitat Pompeu Fabra in Barcelona, Spain. " As

we learn more about how muscles grow in adults, we may uncover new

methods for restoring lost muscle mass in the elderly and ill, " she

added.

Skeletal muscles are made up of individual myofibers, each with many

nuclei containing genetic material. As muscles are made to work

harder, they adapt by bulking up each of those individual fibers,

the researchers explained, but the mechanisms responsible have

largely remained elusive.

Mounting evidence has shown that the growth of myofibers is limited

by the need to maintain an equilibrium between the number of nuclei

and the fibers' overall volume. Because mature myofibers are

incapable of cell division, new nuclei must be supplied by satellite

cells (muscle stem cells). Once activated, satellite cells follow an

ordered set of events, including proliferation, migration, and

incorporation into the myofiber, leading to its growth.

Now, the researchers have found that IL-6 is an essential regulator

in that process. While IL-6 was virtually undetectable in the

muscles of control mice, animals whose muscles were made to work

harder showed an increase in IL-6 after one day. That cytokine rise

was maintained for two weeks before it declined again.

Interestingly, systemically high levels of IL-6 had earlier been

implicated in the muscle wasting process, Muñoz-Cánoves

noted. " Having excess IL-6 is bad, but its local translation is

required for muscle growth. "

The researchers further found that IL-6 was produced both within

myofibers and in their associated satellite cells, leading to muscle

growth. In contrast, the muscles of mice lacking IL-6 did not show

any significant increase in size after several weeks of overloading.

The researchers also showed that IL-6 exerts its effects by inducing

the proliferation of satellite cells.

While Muñoz-Cánoves said that the findings are " just the beginning "

of a new line of investigation into how adult muscle grows, she

added that they might ultimately provide a new avenue for muscle-

building therapies.

" Treatments could be designed to compensate for or block the

pathways leading to muscle loss, " she said. " In muscles that have

already lost mass, you might also be able to stimulate muscle

growth. "