Epidemiology of IGF's and Aging

描述（由主要研究者提供）：胰岛素样生长因子（IGF）系统在不同物种中高度保守，在哺乳动物生命周期的所有阶段（从胎儿发育到儿童期/青春期生长和成年期）中发挥关键作用。胰岛素样生长因子-1（IGF-I）是IGF系统的一种重要肽类激素，参与调节全身组织中的细胞周期-促进细胞增殖和体细胞生长，同时抑制细胞凋亡。在人类中，IGF系统在衰老和与年龄相关的疾病中的作用仍然知之甚少，尽管这一研究领域为通过调节IGF途径减缓衰老过程的新药带来了希望。本研究将评估IGF-I、IGF-I和IGF结合蛋白（IGFBP-1、IGFBP-2、IGFBP-3）的循环水平与老年人的功能限制、残疾、基于身体功能的性能测试、脑形态学变化和生存/寿命的相关性。该研究将使用来自心血管健康研究（CHS）队列的样本和数据-一个大型多中心NIH资助的队列，n= 5，888名65岁或以上的社区居民男性和女性，详细的纵向数据捕获与年龄相关的结果。CHS的随访现已超过15年，这将使我们能够超越任何先前的研究，通过定义重复血液样本中IGF-I和IGFBP水平的个体内轨迹，并将这些测量结果与年龄相关的结果联系起来。进一步的研究将使用全基因组方法鉴定IGF-I和IGFBPs的遗传决定因素，并在Fragrance和鹿特丹队列中进行复制。公共卫生相关性：胰岛素样生长因子（IGF）系统似乎在衰老过程中发挥重要作用。然而，在人类中，IGF系统在衰老和年龄相关疾病中的作用仍然知之甚少。该项目将评估IGF系统与残疾的关系，大脑结构的变化，以及65岁以上男性和女性的长寿，其长期目标是通过调节IGF途径来告知新药的开发，以减缓衰老过程。

DESCRIPTION (provided by principal investigator): 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. PUBLIC HEALTH RELEVANCE: The insulin-like growth factor (IGF) system appears to play a major role in the aging process. However, in humans, the role of the IGF system in aging and age-related diseases is still poorly understood. This project will assess the relationship of the IGF system with disability, changes in brain structure, and longevity among 65+ year old men and women, with the long-term goal of informing the development of new drugs that slow the aging process by modulating IGF pathways.