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生长激素和胰岛素样生长因子-1(IGF-1)的缺乏会缩短还是延长寿命?

Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?

作者信息

Laron Zvi

机构信息

Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center, WHO Collaborating Center for the Study of Diabetes in Youth, Tel Aviv University, Tel Aviv, Israel.

出版信息

Mech Ageing Dev. 2005 Feb;126(2):305-7. doi: 10.1016/j.mad.2004.08.022.

Abstract

Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.

摘要

目前关于生长激素(GH)和胰岛素样生长因子-I(IGF-I)缺乏对衰老和寿命影响的知识存在争议。对因GH基因缺失导致孤立性GH缺乏的未治疗患者、因PROP-1基因突变导致多种垂体激素缺乏的患者以及因GH受体基因缺失或突变(拉伦综合征)导致孤立性IGF-I缺乏的患者进行研究发现,这些患者尽管有早期衰老迹象(皮肤皱纹、肥胖、胰岛素抵抗和骨质减少),但寿命很长,可达80至90岁。遗传性GH缺乏的动物模型,如斯内尔小鼠(Pit-1基因突变)、艾姆斯小鼠(PROP-1基因突变)和拉伦小鼠(GH受体基因敲除),与正常对照相比,在统计学上具有显著更高的寿命。相反,GH转基因小鼠和分泌大量GH的肢端肥大症患者会过早死亡。这些数据提出了一个问题,即与倡导此类疗法的政策相反,对成年人进行药物性GH给药是否有害。

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