Epidemiology of IGF's and Aging

胰岛素样生长因子(IGF)系统在物种间高度保守， 在哺乳动物生命周期的所有阶段，从胎儿发育起，都起着至关重要的作用 通过儿童/青春期的成长和成年。胰岛素样生长因子-1(IGF-I)， IGF系统中的一种重要的多肽激素，参与调节细胞周期-- 在组织中促进细胞增殖和躯体生长，抑制细胞凋亡 遍及全身。在人类中，IGF系统在衰老和与年龄相关的过程中的作用 人们对疾病的了解仍然很少，尽管这一领域的研究带来了希望 通过调节胰岛素样生长因子途径延缓衰老过程的新药。现在 研究将评估循环中IGF-I、IGF-I和IGF结合水平之间的关系 蛋白质(IGFBP-1、IGFBP-2、IGFBP-3)具有功能缺陷、残疾、 基于表现的身体功能测试，大脑形态变化，以及 老年人的生存/寿命。这项研究将使用来自 心血管健康研究(CHS)队列-由美国国立卫生研究院资助的大型多中心队列 N=5,888名65岁或65岁以上的社区居民，详细说明 获取与年龄相关的结果的纵向数据。CHS的随访现已超过15人 年，这将使我们能够超越任何先前的研究，通过定义个人内部 重复采集血样中胰岛素样生长因子-I和胰岛素样生长因子结合蛋白的变化轨迹及其相互关系 测量与年龄相关的结果。进一步的研究将确定基因 使用全基因组方法研究IGF-I和IGFBPs的决定因素，并在 弗雷明翰和鹿特丹的队伍。 11/3/2008 1 K：\PI_Administration\Kaplan\2008年11月5日版本\Abstract_Oct08.doc 创建于10/31/2008 10：45：00 AM

The insulin-like growth factor (IGF) system is highly conserved across species and plays a critical role in all phases of the mammalian life cycle, from fetal development through childhood / pubertal growth and adulthood. Insulin-like growth factor-1 (IGF-I), an important peptide hormone of the IGF system, is involved in regulation cell cycle - promoting cell proliferation and somatic growth while inhibiting apoptosis - in tissues throughout the body. In humans, the role of the IGF system in aging and age-related diseases is still poorly understood, though this field of research has raised hopes for new drugs that slow the aging process by modulating IGF pathways. The present study will assess the association of circulating levels of IGF-I, IGF-I, and IGF binding proteins (IGFBP-1, IGFBP-2, IGFBP-3) with functional limitation, disability, performance-based tests of physical function, brain morphologic changes, and survival/longevity among older adults. The study will use specimens and data from the Cardiovascular Health Study (CHS) cohort - a large multi-center NIH-funded cohort of n=5,888 community-dwelling men and women 65 years or older, with detailed longitudinal data capturing age-related outcomes. Follow-up in CHS is now over 15 years, which will allow us to go beyond any prior studies by defining within-individual trajectories of IGF-I and IGFBP levels from repeated blood samples, and relating these measurements to age-related outcomes. Further studies will identify genetic determinants of IGF-I and IGFBPs using a whole-genome approach, with replication in the Framingham and Rotterdam cohorts. 11/3/2008 1 K:\PI_Administration\Kaplan\Nov 5 2008 revision\Abstract _ Oct08.doc Created on 10/31/2008 10:45:00 AM