Previous research shows that healthy older people have slower rates of myofibrillar protein synthesis than young adults. This change in protein synthesis could have adverse effects on muscle mass and function. Restoring a more youthful rate of myofibrillar protein synthesis potentially could help to minimize the muscle atrophy associated with aging. Because aging also is associated with decreased production of gonadal steroids, and because there is evidence that gonadal steroids could have anabolic effects in muscle, studies will be done to examine the effects of gonadal steroid replacement on myofibrillar protein metabolism in healthy volunteers over 60 years old. The studies are designed to test several hypotheses: that testosterone replacement stimulates myofibrillar protein synthesis in men with low non-SHBG-bound testosterone levels; that blocking conversions of testosterone to dihydrotestosterone does not inhibit the anabolic effect of testosterone to dihydrotestosterone does not inhibit the anabolic effect of testosterone; that estrogen replacement stimulates myofibrillar protein synthesis in postmenopausal women; that giving progestin along with the estrogen replacement attenuates the effect of estrogen; that testosterone stimulates myofibrillar protein synthesis in postmenopausal women (with a smaller dose than that given to men); that gonadal steroids increase tissue levels of the mRNAs that encode the abundant myofibrillar proteins. Myofibrillar protein synthesis will be determined by incorporation of a stable isotope tracer. Myofibrillar degradation will be determined by 3-methylhistidine excretion. Levels of mRNAs will be determined by hybridizing muscle RNA with specific antisense RNA probes. The basic knowledge gained in this study could help to elucidate whether gonadal steroids could be useful as part of a comprehensive strategy to prevent or reverse muscle atrophy in old age.
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