- NEW YORK (Reuters Health) -- An experimental gene therapy appears to reverse
age-related loss of muscle in mice, and may do the same in humans, researchers
report.
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- These findings could eventually lead
to treatments for age-related frailty, and, possibly, for muscle-wasting
disorders such as muscular dystrophies, according to Dr. H. Lee Sweeney,
and colleagues at the University of Pennsylvania Medical School in Philadelphia.
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- Most mammals -- mice and men alike --
lose up to a third of their muscle mass and strength as they age. It is
not clear why this happens. But evidence suggests that declines in the
production and activity of growth hormone (GH) and insulin-like growth
factors (IGF) -- hormones that influence the growth and repair of muscle
cells -- play a key role. In previous studies, animals given GH added muscle
mass, but did not gain strength.
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- To see whether IGF might prompt an increase
in both muscle mass and strength, Sweeney and colleagues studied its effects
in young and old mice. Using gene therapy techniques, the researchers stripped
a virus of its disease-causing genes, and substituted the genes for IGF
factor-I (IGF-I) and a muscle-promoting enzyme called myosin light chain
(MLC). They then injected the virus into each mouse's muscle fibers.
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- Four months after treatment, young adult
mice -- those 6-months old -- showed a 15% increase in the mass of muscles
treated with IGF-I. Elderly mice -- 27-months old -- had a 19% increase
in muscle mass, according to Sweeney and colleagues. Moreover, muscle strength
increased by 14% in young mice and 27% in older mice, they report. The
findings were presented Monday at the annual meeting of the American Society
for Cell Biology in San Francisco, California, and will be published later
this month in the Proceedings of the National Academy of Sciences.
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- ``The results of this study demonstrate
that IGF-I overexpression in muscle can preserve the morphological and
functional characteristics of the skeletal muscles of old mice such that
they are equivalent to those of young adult muscles,'' Sweeney and colleagues
write.
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- Injections of the genetically altered
virus appeared to increase IGF-I levels only in the muscles, the researchers
report. ``This is an important advantage... since elevation of IGF-I levels
in the blood could lead to undesirable effects in other tissues,'' they
add.
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- The increased levels of IGF-I appeared
to prevent age-related muscle loss at least partly by stimulating special
cells called satellite cells that repair muscle damaged during use, the
researchers speculate.
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- ``Based on these results, we further
hypothesize that the primary cause of the aging-related loss in strength...
is a failure to activate satellite cells in order to repair cumulative
injury that results from normal muscle utilization,'' they write.
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- Since age-related changes in muscle are
similar to early changes in muscle seen in patients with muscular dystrophy,
it is possible that a similar gene therapy approach ``may form the basis
for gene therapy for both aging-related loss of muscle function and impairments
associated with muscle disease,'' the researchers write.
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- ``However,'' they add, ``this work raises
a number of ethical considerations about the use of IGF-I in gene therapy,
as its beneficial effects could be used in humans for athletic or cosmetic
purposes, rather than for disease treatment.''
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