Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function

During the aging process, mammals lose up to a third of their skeletal musc le mass and strength. Although the mechanisms underlying this loss are not entirely understood, we attempted to moderate the loss by increasing the re generative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth fac tor I (IGF-I) in differentiated muscle fibers, We demonstrate that the IGF- I expression promotes an average increase of 15% in muscle mass and a 14% i ncrease in strength in young adult mice, and remarkably, prevents aging-rel ated muscle changes in old adult mice, resulting in a 27% increase in stren gth as compared with uninjected old muscles. Muscle mass and fiber type dis tributions were maintained at levels similar to those in young adults. We p ropose that these effects are primarily due to stimulation of muscle regene ration via the activation of satellite cells by IGF-I, This supports the hy pothesis that the primary cause of aging-related impairment of muscle funct ion is a cumulative failure to repair damage sustained during muscle utiliz ation. Our results suggest that gene transfer of IGF-I into muscle could fo rm the basis of a human gene therapy for preventing the loss of muscle func tion associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated.