Nass Ralf, Farhy Leon S, Liu Jianhua, Pezzoli Suzan S, Johnson Michael L, Gaylinn Bruce D, Thorner Michael O
Division of Endocrinology and Metabolism (R.N., L.S.F., J.L., S.S.P., B.D.G., M.O.T.), Department of Medicine, Center for Diabetes Technology (L.S.F.), and Department of Pharmacology (M.L.J.), University of Virginia, Charlottesville, Virginia 22908.
J Clin Endocrinol Metab. 2014 Feb;99(2):602-8. doi: 10.1210/jc.2013-3158. Epub 2013 Nov 27.
Acyl-ghrelin is thought to have both orexigenic effects and to stimulate GH release. A possible cause of the anorexia of aging is an age-dependent decrease in circulating acyl-ghrelin levels.
The purpose of the study was to compare acyl-ghrelin and GH concentrations between healthy old and young adults and to examine the relationship of acyl-ghrelin and GH secretion in both age groups.
Six healthy older adults (age 62-74 y, body mass index range 20.9-29 kg/m(2)) and eight healthy young men (aged 18-28 y, body mass index range 20.6-26.2 kg/m(2)) had frequent blood samples drawn for hormone measurements every 10 minutes for 24 hours. Ghrelin was measured in an in-house, two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in a sensitive assay (Immulite 2000), and GH peaks were determined by deconvolution analysis. The acyl-ghrelin/GH association was estimated from correlations between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-minute interval preceding each GH burst.
Twenty-four-hour mean (±SEM) GH (0.48 ± 0.14 vs 2.2 ± 0.3 μg/L, P < .005) and acyl-ghrelin (14.7 ± 2.3 vs 27.8 ± 3.9 pg/mL, P < .05) levels were significantly lower in older adults compared with young adults. Twenty-four-hour cortisol concentrations were higher in the old than the young adults (15.1 ± 1.0 vs 10.6 ± 0.9 μg/dL, respectively, P < .01). The ghrelin/GH association was more than 3-fold lower in the older group compared with the young adults (0.16 ± 0.12 vs 0.69 ± 0.04, P < .001).
These results provide further evidence of an age-dependent decline in circulating acyl-ghrelin levels, which might play a role both in the decline of GH and in the anorexia of aging. Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are less tightly linked to GH regulation.
酰基胃饥饿素被认为具有促食欲作用并能刺激生长激素(GH)释放。衰老所致厌食的一个可能原因是循环中酰基胃饥饿素水平随年龄增长而下降。
本研究旨在比较健康老年人与年轻人之间的酰基胃饥饿素和GH浓度,并探讨两个年龄组中酰基胃饥饿素与GH分泌的关系。
6名健康老年人(年龄62 - 74岁,体重指数范围20.9 - 29 kg/m²)和8名健康年轻男性(年龄18 - 28岁,体重指数范围20.6 - 26.2 kg/m²)在24小时内每10分钟采集一次血样用于激素检测。采用针对全长酰基胃饥饿素的内部双位点夹心酶联免疫吸附测定法(ELISA)检测胃饥饿素。采用灵敏检测法(Immulite 2000)检测GH,并通过去卷积分析确定GH峰值。根据各个GH分泌事件的幅度与每次GH脉冲前60分钟间隔内的平均酰基胃饥饿素浓度之间的相关性来估计酰基胃饥饿素/GH的关联。
与年轻人相比,老年人的24小时平均(±标准误)GH水平(0.48 ± 0.14 vs 2.2 ± 0.3 μg/L,P <.005)和酰基胃饥饿素水平(14.7 ± 2.3 vs 27.8 ± 3.9 pg/mL,P <.05)显著较低。老年人的24小时皮质醇浓度高于年轻人(分别为15.1 ± 1.0 vs 10.6 ± 0.9 μg/dL,P <.01)。与年轻人相比,老年组中胃饥饿素/GH的关联降低了3倍多(0.16 ± 0.12 vs 0.69 ± 0.04,P <.001)。
这些结果进一步证明了循环中酰基胃饥饿素水平随年龄增长而下降,这可能在GH下降和衰老所致厌食中均起作用。我们的数据还表明,随着正常衰老,内源性酰基胃饥饿素水平与GH调节的联系不再紧密。