Hormonal trajectories in aging

描述（由申请人提供）：代谢调节对于体内平衡和面对外部威胁的恢复力至关重要。激素在代谢调节中起着关键作用，因此，在维持自我平衡的弹性。虽然很明显，许多激素下降，随着年龄的增长，在人口水平上，涉及多个时间点的个人轨迹的分析从来没有进行过。因此，个人轨迹的预测价值问题仍然没有答案。IGF-1和DHEAS代表了轨迹分析的优秀候选者：每一个都对应于不同的激素途径;两者对功能性衰老的关键生理系统都有不同的影响（例如，心血管、肌肉骨骼和神经系统）;并且在人群水平上，两者都随着年龄的增长而下降。我们的中心假设是，IGF-1和DHEAS的变化轨迹单独和联合预测老年人的健康，功能和生存。我们建议使用来自心血管健康研究（CHS）的数据来评估这一假设，CHS是一项已建立的、特征良好的、前瞻性的、NIH赞助的对65岁以上社区居民男性和女性的纵向研究。在16年的随访期内收集的现有数据以及该时间跨度内8个时间点的库存血液样本可用于拟议的分析。我们假设，那些随着时间的推移激素水平没有下降的人将比那些轨迹显示整体下降的人和那些激素水平随时间变化的人有更大的生存率和更高的功能水平。本研究提出以下研究目标：1）确定IGF-1和DHEAS的主要轨迹模式的流行率，并确定每种轨迹模式与健康和存活率的关联，2）确定男性和女性在其轨迹模式中的差异，3）确定单独的基线值，单独的独立轨迹，或独立轨迹加基线值是健康和存活的最佳预测因子，4）定义不良事件和运动对轨迹的影响，和5）确定关节异常对IGF-1和DHEAS轨迹模式的影响。这项研究是一个新的应用内分泌模型的稳态和轨迹分析，研究生物老龄化的人口水平。我们的工作将直接指导生长激素类似物和DHEA的适当人群的选择。

DESCRIPTION (provided by applicant): Metabolic regulation is essential for homeostasis and for resilience in the face of external threats. Hormones play key roles in metabolic regulation, and, therefore, in maintaining homeostatic resilience. Although it is clear that many hormones decline with increasing age at the population level, analysis of individual trajectories involving multiple timepoints has never been performed. Therefore, the question of the predictive value of individual trajectories remains unanswered. IGF-1 and DHEAS represent excellent candidates for trajectory analysis: each corresponds to a distinct hormonal pathway; both have diverse effects on physiologic systems critical for functional aging (e.g., cardiovascular, musculoskeletal, and neurologic); and both, at the population level, decrease with age. Our central hypothesis is that trajectories of change in IGF-1 and DHEAS individually and jointly predict health, function, and survival in old age. We propose to evaluate this hypothesis using data from the Cardiovascular Health Study (CHS), an established, well-characterized, prospective, NIH-sponsored longitudinal study of community-dwelling men and women over the age of 65. Existing data collected over a 16-year follow-up period, with banked blood specimens at eight timepoints over this time span, are available for the proposed analyses. We hypothesize that those who have no decline in their hormonal levels over time will have greater survival and retain higher levels of function with aging than those whose trajectory demonstrates an overall decline and those who have extreme variability in hormonal levels overtime. This study proposes the following research aims: 1) to define the prevalence of the predominant patterns of trajectories of IGF-1 and DHEAS and to determine the association of each trajectory pattern with health and survival, 2) to determine differences between men and women in their trajectory patterns, 3) to establish whether the baseline values alone, the independent trajectories alone, or the independent trajectories plus the baseline values are the best predictors of health and survival, 4) to define the impact of adverse events and exercise on the trajectory, and 5) to determine the impact of joint abnormalities in trajectory patterns of IGF-1 and DHEAS. This research is a novel application of endocrine models of homeostasis and trajectory analysis to studying the biology of aging at the population level. Our work will directly guide the selection of the appropriate population for growth hormone analogues and DHEA.