GROWTH FACTORS AND EXERCISE IN OLDER WOMEN

衰老与肌肉质量、力量和 耐力，而脂肪团(尤其是中心性肥胖症)与 代谢异常增加。这些与年龄相关的变化可能 对身体机能有深远的影响，容易产生依赖。 最近的一项研究发现，脱脂质量、脂肪质量、 生长激素(GH)缺乏老年男性的骨量和皮肤厚度 经过6个月的皮下注射重组生长激素。这个 对那项研究的解释受到未能衡量变化的限制 在力量、耐力、脂肪分布和机能状态或 仔细记录治疗的代谢副作用。此外， 研究是在生长激素缺乏的男性中进行的，这是这些人中的一小部分 老年人有虚弱的危险。 我们建议使用前瞻性、随机化、双盲、部分 在一组尚未虚弱的女性中进行析因研究设计： (1)评估6个月的积极和消极的生理影响 单独应用合成生长激素释放激素(GHRH)干预 或结合耐力(ET)或力量(ST)训练； 确定GHRH给药之间是否存在潜在的治疗关系 和锻炼，包括相加效应或锻炼的能力 减轻代谢副作用；(3)确定ST是否可以单独 保持最初6个月单独使用GHRH或 结合ST；(4)评估任何观察到的生理 改善转化为身体机能状态的可衡量的收益。 我们选择使用GHRH而不是GH，因为它的尺寸较小 潜在地使其生产成本更低，更有可能被管理 口服或鼻腔注射。更重要的是，有证据表明皮下注射 服用GHRH与恢复更具生理性的 年轻和老年受试者的搏动性生长激素反应。 我们假设：1)运动(ET或ST)或GHRH管理 会改善力量、身体成分和机能，而运动再加上 GHRH将是相加的；2)ET将在更大程度上缓解任何 胰岛素抵抗与GHRH有关，而ST会产生 在力量和脱脂质量方面有更大的增长；3)6)后的改善 GHRH单独或GHRH加ST的月份将可通过 4)GHRH后的生理收益， 锻炼或联合锻炼将转化为可衡量的改善 功能性能。

Aging is associated with reductions in muscle mass, strength, and endurance, while fat mass (especially central adiposity) and the associated metabolic abnormalities are increased. These "age related" changes may have profound effects on physical function and predispose to dependence. A recent study found significant improvements in fat free mass, fat mass, bone mass and skin thickness in older growth hormone (GH) deficient men following six months of subcutaneous recombinant GH administration. The interpretation of that study is limited by its failure to measure changes in strength, endurance, distribution of fat, and function status or to carefully document the metabolic side effects of therapy. Furthermore, the study was conducted in GH deficient males, a small subpopulation of those elders at risk for frailty. We propose to use a prospective, randomized, double blinded, partial factorial study design in a group of women who are not already frail to: (1) assess the positive and negative physiologic effects of a 6 month intervention with synthetic growth hormone releasing hormone (GHRH) alone or in combination with either endurance (ET) or strength (ST) training; (2) define any potential therapeutic relationships between GHRH administration and exercise, including additive effects or the ability of exercise to mitigate metabolic side effects; (3) determine whether ST alone can maintain any benefits attained in the initial 6 month use of GHRH alone or in combination with ST; (4) assess how any observed physiologic improvements translate into measurable gains in physical functional status. We have chosen to use GHRH instead of GH because its smaller size potentially make it cheaper to produce, and more likely to be administered orally or nasally. More importantly, there is evidence that subcutaneous administration of GHRH is associated with restoration of a more physiologic pulsatile GH response in young and older subjects. We hypothesize that: 1) both exercise (ET or ST) or GHRH administration will improve strength body composition and function, and that exercise plus GHRH will be additive; 2) ET will, to a greater extent, mitigate any insulin resistance observed associated with GHRH, while ST will produce greater gains in strength and fat free mass; 3) the improvements after 6 months of GHRH alone or GHRH plus ST will be maintainable with an additional 6 months of ST alone; 4) the physiologic gains following GHRH, exercise or the combination will translate into measurable improvement in functional performance.