Division of Gerontology and Geriatric Medicine, Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22272-7. doi: 10.1073/pnas.1016369107. Epub 2010 Dec 6.
Both deficiency and excess of growth hormone (GH) are associated with increased mortality and morbidity. GH replacement in otherwise healthy subjects leads to complications, whereas individuals with isolated GH deficiency such as Laron dwarfs show increased life span. Here, we determined the effects of treatment with the GH-releasing hormone (GHRH) receptor antagonist MZ-5-156 on aging in SAMP8 mice, a strain that develops with aging cognitive deficits and has a shortened life expectancy. Starting at age 10 mo, mice received daily s.c. injections of 10 μg/mouse of MZ-5-156. Mice treated for 4 mo with MZ-5-156 showed increased telomerase activity, improvement in some measures of oxidative stress in brain, and improved pole balance, but no change in muscle strength. MZ-5-156 improved cognition after 2 mo and 4 mo, but not after 7 mo of treatment (ages 12, 14 mo, and 17 mo, respectively). Mean life expectancy increased by 8 wk with no increase in maximal life span, and tumor incidence decreased from 10 to 1.7%. These results show that treatment with a GHRH antagonist has positive effects on some aspects of aging, including an increase in telomerase activity.
生长激素（GH）缺乏和过剩都与死亡率和发病率的增加有关。在其他健康受试者中进行 GH 替代会导致并发症，而患有孤立性 GH 缺乏症（如 Laron 侏儒症）的个体则表现出寿命延长。在这里，我们确定了用 GH 释放激素（GHRH）受体拮抗剂 MZ-5-156 治疗 SAM P8 小鼠衰老的效果，该品系随着衰老出现认知缺陷，预期寿命缩短。从 10 月龄开始，每天给小鼠皮下注射 10μg/只 MZ-5-156。用 MZ-5-156 治疗 4 个月的小鼠表现出端粒酶活性增加、大脑某些氧化应激指标改善和杆平衡改善，但肌肉力量没有变化。MZ-5-156 在 2 个月和 4 个月后改善了认知，但在 7 个月（分别为 12、14 和 17 月龄）的治疗后没有改善。平均预期寿命增加了 8 周，最大预期寿命没有增加，肿瘤发病率从 10%降至 1.7%。这些结果表明，用 GHRH 拮抗剂治疗对衰老的某些方面具有积极影响，包括端粒酶活性的增加。
