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New England Journal of Medicine, Volume 323 July 5, 1990 Number 1
Daniel Rudman, M.D., Axel G. Feller, M.D., Hoskote S. Nagraj, M.D., Gregory A. Gergans, M.D., Pardee Y. Lalitha, M.D., Allen F. Goldberg, D.D.S., Robert A. Schlenker, Ph.D., Lester Cohn, M.D., Inge W. Rudman, B.S., and Dale E. Mattson, Ph.D.
Abstract Background. Thedeclining activity of the growth hormone-insulin-like growth factor 1 (IGF-1) axis with advancing age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging.
Methods. To test this hypothesis, we studied IGF-1 plasma with 21 healthy men from 61 to 81 years old who had plasma IGF-1 concentrations of less than 350 U per liter during a six-monthbase-line period and a six-month treatment period that followed. During the treatment period, 12 men (group 1) received approximately 0.03 mg of biosynthetic human growth hormone per kilogram of body weight subcutaneously three times a week, and 9 men (group 2) received no treatment. Plasma IGF-1 levels were measured monthly. At the end of each period, we measured lean body mass, the mass of adiposetissue, skin thickness (epidermis plus dermis), and bone density at nine skeletal sites.
Results. In group 1, the mean plasma IGF-1 level rose into the youthful range of 500 to 1500 U per liter during treatment, whereas in group 2 it remained below 350 U per liter. The administration of human growth hormone for six months in group 1 was accompanied by an 8.8 percent increase in lean body mass, a14.4 percent decrease in adipose-tissue mass, and a 1.6 percent increase in average lumbar vertebral bone density (P
Conclusions. Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occurs in old age. (New England Journal of Medicine, 1990; 323:1-6).
In middle and lateadulthood, all people experience a series of progressive alterations in body composition. The lean body mass shrinks and the mass of adipose tissue expands. The contraction in lean body mass reflects atrophic processes in skeletal muscle, liver, kidney, spleen, skin, and bone.
These structural changes have been considered unavoidable results of aging. It has recently been proposed, however, that reducedavailability of growth hormone in late adulthood may contribute to such changes. This proposal is based on two lines of evidence. First, after about the age of 30, the secretion of growth hormone by the pituitary gland tends to decline. Since growth hormone is secreted in pulses, mostly during the early hours of sleep, it is difficult to measure the 24-hour secretion of the substance directly.Growth hormone secretion can be measured indirectly, however measure the 24-hour secretion of the substance measure the 24-hour secretion of the substance directly. Growth hormone secretion can be measured indirectly, however, by measuring the plasma concentration of insulin-like growth factor I (IGF-I, also known as somatomedin C), which is produced and released by the liver and perhaps other tissuesin response to growth hormone. There is little diurnal variation in the plasma IGF-I concentration, and measurements of it are therefore a convenient indicator of growth hormone secretion. Plasma IGF-I concentrations decline with advancing age in healthy adults. Less than 5 percent of the healthy men 20 to 40 years old have plasma IGF-I values of less than 350 U per liter, but the values arebelow this figure in 30 percent of the healthy men over 60. Likewise, the nocturnal pulses of growth hormone secretion becomes smaller or disappear with advanced age. If the plasma concentration of IGF-I falls below 350 U per liter in older adults, no spontaneous circulating pulses of growth hormone can be detected by currently available radioimmunoassay methods. The concomitant decline in plasma...
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