The IGF-I response to very low rhGH doses is preserved in human ageing

OBJECTIVES The activity of the GH/IGF-I axis varies during life and is clea rly reduced in the elderly. In fact, GH, IGF-I and IGFBP-3 levels in older people are clearly reduced and similar to those observed in patients with G H deficiency. The declining activity of the GH/IGF-I axis with advancing ag e may contribute to changes in body composition, structure, function and me tabolism. In fact, treatment with pharmacological doses of rhGH restored pl asma IGF-I levels, increased lean body mass and muscle strength while decre ased adipose tissue mass in healthy elderly subjects. At present it is uncl ear whether peripheral GH sensitivity is preserved in aging. To clarify thi s point, we aimed to verify the effect of both single dose and short term t reatment with very low rhGH doses on the IGF-I levels in normal elderly sub jects. Normal young adults were studied as controls. DESIGN We studied the IGF-I response to rhGH administration after single (2 0 mu g/kg s.c.) or repeated administrations (5 mu g/kg s.c. for 4 days) in two groups of young and elderly subjects. SUBJECTS Twenty-seven healthy elderly (ES, 14F and 13M, age mean +/- SEM: 6 9.4 +/- 1.3 years, BMI: 23.9 +/- 0.5 kg/m(2)) and 21 young adult subjects ( YS, 12 F and 9 M, 29.8 +/- 1.2 years, 23.8 +/- 0.5 kg/m(2)) were studied, d ivided into two groups. MEASUREMENTS Group 1: blood samples for IGF-I and IGFBP-3 assay were drawn basally and 12 h after rhGH administration (20 mu g/kg). Group 2: blood sam ples for IGF-I, IGFBP-3, glucose and insulin assays were drawn basally, 12 h after the first and the last rhGH administration (5 mu g/kg). Free T3 (fT 3), free T4 (fT4) and TSH levels were also assayed basally and after the la st rhGH administration; oestradiol and testosterone levels were measured ba sally. RESULTS Basal IGF-I levels were lower in ES (whole group) than in YS (whole group) (123.1 +/- 8.9 vs. 230.4 +/- 16.1 mu g/l, P < 0.001) while IGFBP-3 levels in the two groups were similar (2.7 +/- 0.2 vs. 3.1 +/- 0.2 mg/l). N o sex-related differences in IGF-I and IGFBP-3 levels were recorded in eith er group. Group 1: the single administration of 20 mu g/kg rhGH induced a s ignificant (P < 0.001) IGF-I rise both in YS (318.0 +/- 25.3 vs. 256.0 +/- 21.6 mu g/l) and ES (187.2 +/- 16.8 vs. 100.4 +/- 9.5 mu g/l). IGF-I levels after rhGH in ES persisted lower than those in YS (P < 0.001), but the per centage IGF-I increase after rhGH was higher (P < 0.001) in ES (91.6 +/- 12 .9%) than in YS (23.9 +/- 5.0%) subjects. Both in YS and ES IGFBP-3 levels were significantly increased to the same extent by 20 mu g/kg rhGH (3.0 +/- 0.2 vs. 2.3 +/- 0.2 mg/l; 2.9 +/- 0.2 vs. 2.6 +/- 0.2 mg/l, P < 0.001 vs. baseline). Group 2: basal glucose, insulin, fT3, fT4 and TSH levels in YS a nd ES were similar; testosterone levels in aged and young men were similar while oestradiol levels in aged women were lower (P < 0.01) than in the you ng ones. IGF-I levels were significantly increased 12 h after the first adm inistration of 5 mu g/kg rhGH both in ES (166.6 +/- 15.7 vs. 138.3 +/- 12.1 mu g/l, P < 0.03) and YS (272.2 +/- 16.1 vs. 230.4 +/- 16.1 mu g/l, P < 0. 001). Twelve hours after the last rhGH administration IGF-I levels were fur ther increased (P < 0.001) both in ES (208.7 +/- 21.1 mu g/l) and YS (301.7 +/- 17.6 mu g/l). IGF-I levels in ES persisted lower than those in YS at e ach time point (P < 0.001); however, the percentage IGF-I increase after rh GH in ES and YS was similar (after the first administration: 22.4 +/- 5.1 v s. 21.7 +/- 5.1%; after the last administration: 52.9 +/- 9.5 vs. 39.5 +/- 9.9%). No significant variation in IGFBP-3, glucose, insulin, fT3, fT4 or T SH levels was recorded in either ES or YS. CONCLUSIONS Our data demonstrate that IGF-I levels in aging are reduced but the peripheral sensitivity to rhGH is preserved. In fact, in aged subjects the percentage rhGH-induced IGF-I increase is similar or even higher than that in young controls. Our findings also indicate that a very low rhGH dos e is needed in aged subjects to restore IGF-I levels to the young range.