Turning The Clock Back on Aging Muscles
Scientists have found and manipulated body chemistry linked
to the aging of muscles and were able to turn back the clock on
old human muscle, restoring its ability to repair and rebuild
itself, they said today.
The study involved a small number of participants, however. And
the news is not all rosy.
Importantly, the research also found evidence that aging muscles
need to be kept in shape, because long periods of atrophy are
more challenging to overcome. Older muscles do not respond as
well to sudden bouts of exercise, the scientists discovered. And
rather than building muscle, an older person can generate scar
tissue upon, say, lifting weights after long periods of inactivity.
The findings are detailed today in the European journal EMBO
"Our study shows that the ability of old human muscle to
be maintained and repaired by muscle stem cells can be restored
to youthful vigor given the right mix of biochemical signals,"
said study leader Irina Conboy of the University of California,
Berkeley. "This provides promising new targets for forestalling
the debilitating muscle atrophy that accompanies aging, and perhaps
other tissue degenerative disorders as well."
More research would be needed before any anti-aging products
might result from the work, however.
Scientists know that muscles deteriorate rapidly in old age.
Mechanisms that prevent muscle breakdown work less effectively
in people over the age of 65, a study earlier this month found.
Other research has shown that neurons have to yell louder to kick
aging muscles into gear.
Yet much about how and why muscles respond to exercise, and atrophy
without it, remains unknown.
Previous research in animal models led by Conboy revealed that
the ability of adult stem cells to do their job of repairing and
replacing damaged tissue is governed by the molecular signals
they get from surrounding muscle tissue, and that those signals
change with age in ways that thwart tissue repair. But the animal
studies also showed that the regenerative function in old stem
cells can be revived.
Meanwhile, there is no fountain of youth for aging muscles. The
best advice for now: Eat well and exercise regularly throughout
Human muscle atrophy
In the new study, a team of researchers compared samples of muscle
tissue from nearly 30 healthy men. The young group ranged from
age 21 to 24 and averaged 22.6 years old, while the older group
averaged 71.3 years old, ranging from 68 to 74.
Muscle biopsies were taken from one quadriceps (upper leg muscle)
of each test subject, who then had that leg immobilized in a cast
for two weeks to simulate muscle atrophy. After the casts were
removed, the men lifted weights to regain muscle mass. More muscle
tissue samples were taken.
Analysis showed that before the legs were immobilized, the adult
stem cells responsible for muscle repair and regeneration were
only half as numerous in the old muscle as they were in young
tissue. (Muscle stem cells produce other muscle cells.) The disparity
increased during exercise, with younger tissue having four times
more regenerative cells compared with the old muscle.
Muscles of the older participants showed signs of inflammation
and scar tissue formation during immobility and again four weeks
after the cast was removed.
"Two weeks of immobilization only mildly affected young
muscle, in terms of tissue maintenance and functionality, whereas
old muscle began to atrophy and manifest signs of rapid tissue
deterioration," said Morgan Carlson, another UC Berkeley
researcher and the study's lead author.
"The old muscle also didn't recover as well with exercise,"
Carlson said. "This emphasizes the importance of older populations
staying active because the evidence is that for their muscle,
long periods of disuse may irrevocably worsen the stem cells'
The researchers warned that in the elderly, rigorous exercise
after immobility can cause replacement of functional muscle by
scarring and inflammation.
"It's like a Catch-22," Conboy said.
Previous studies have shown that adult muscle stem cells have
a receptor called Notch, which triggers growth when activated.
Those stem cells also have a receptor for the protein TGF-beta
that, when excessively activated, sets off a chain reaction that
ultimately inhibits a cell's ability to divide. In aging mice,
the decline of Notch and increased levels of TGF-beta ultimately
block the stem cells' ability to rebuild muscle.
The new study found the same process at work in humans. But it
also revealed that an enzyme called mitogen-activated protein
kinase (MAPK) regulates Notch activity.
In old muscle, MAPK levels are low, so the Notch pathway is not
activated and the stem cells no longer perform their muscle regeneration
jobs properly, the researchers said.
In the lab, the researchers cultured old human muscle and forced
the activation of MAPK. The regenerative ability of the old muscle
was significantly enhanced, they report.
"In practical terms, we now know that to enhance regeneration
of old human muscle and restore tissue health, we can either target
the MAPK or the Notch pathways," Conboy said. "The ultimate
goal, of course, is to move this research toward clinical trials."
The research was supported by the National Institutes of Health,
the California Institute of Regenerative Medicine, the Danish
Medical Research Council and the Glenn Foundation for Medical