Aging News & Information
Aging Muscles May Be Restored by Discovery of a Key
to Making Muscle
Results hailed as important step toward developing
new muscle to treat muscle diseases; good news for seniors with muscles
wasting away from aging
8, 2014 – Promising results have been achieved in repairing damaged
tissue in muscles which could lead to a new therapeutic approach to
treating the millions of people suffering from muscle diseases,
including those with muscular dystrophies and muscle wasting associated
with cancer and aging seniors, according to the study, published
September 7 in Nature
Researchers at Sanford-Burnham Medical Research
Institute (Sanford-Burnham) in La Jolla, California, have developed this
novel technique to promote tissue repair in damaged muscles. The
technique also creates a sustainable pool of muscle stem cells needed to
support multiple rounds of muscle repair.
There are two important processes that need to
happen to maintain skeletal-muscle health. First, when muscle is damaged
by injury or degenerative disease such as muscular dystrophy, muscle
stem cells—or satellite cells—need to differentiate into mature muscle
cells to repair injured muscles.
Second, the pool of satellite cells needs to be
replenished so there is a supply to repair muscle in case of future
injuries. In the case of muscular dystrophy, the chronic cycles of
muscle regeneration and degeneration that involve satellite-cell
activation exhaust the muscle stem-cell pool to the point of no return.
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"Our study found that by introducing an inhibitor
of the STAT3 protein in repeated cycles, we could alternately replenish
the pool of satellite cells and promote their differentiation into
muscle fibers," said Alessandra Sacco, Ph.D., assistant professor in the
Development, Aging, and Regeneration Program at Sanford-Burnham.
"Our results are important because the process
works in mice and in human muscle cells."
"Our next step is to see how long we can extend the
cycling pattern, and test some of the STAT3 inhibitors currently in
clinical trials for other indications such as cancer, as this could
accelerate testing in humans," added Sacco.
"These findings are very encouraging. Currently,
there is no cure to stop or reverse any form of muscle-wasting
disorders—only medication and therapy that can slow the process," said
Vittorio Sartorelli, M.D., chief of the Laboratory of Muscle Stem Cells
and Gene Regulation and deputy scientific director at the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
"A treatment approach consisting of cyclic bursts
of STAT3 inhibitors could potentially restore muscle mass and function
in patients, and this would be a very significant breakthrough."
Revealing the mechanism of
STAT3 (signal transducer and activator of
transcription 3) is a protein that activates the transcription of genes
in response to IL-6, a signaling protein released by cells in response
to injury and inflammation. Prior to the study, scientists knew that
STAT3 played a complex role in skeletal muscle, promoting tissue repair
in some instances and hindering it in others. But the precise mechanism
of how STAT3 worked was a mystery.
The research team first used normally aged mice and
mice models of a form of muscular dystrophy that resembles the human
disease to see what would happen if they were given a drug to inhibit
STAT3. They found that the inhibitor initially promoted satellite-cell
replication, followed by differentiation of the satellite cells into
muscle fibers. When they injected the STAT3 inhibitor every seven days
for 28 days, they found an overall improvement in skeletal-muscle
repair, and an increase in the size of muscle fibers.
"We were pleased to find that we achieved similar
results when we performed the experiments in human muscle cells," said
Sacco. "We have discovered that by timing the inhibition of STAT3 - like
an "on/off" light switch - we can transiently expand the satellite-cell
population followed by their differentiation into mature muscle cells."
This work was supported by U.S. National Institutes
of Health (NIH), Sanford-Burnham Center, California Institute for
Regenerative Medicine Training, and a grant from the Italian Foreign