Gene Therapy Reverses
Age-Related Muscle Loss
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.
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.
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.
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.
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.
``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.
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.
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.
``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.
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.
``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.''