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能力至关重要。激素在代谢调节中起着关键作用，因此，在维持体内平衡弹性中起着关键作用。虽然很明显，在人口水平上，许多激素随着年龄的增长而下降，但从未对涉及多个时间点的个体轨迹进行过分析。因此，个体轨迹的预测价值问题仍然没有答案。IGF-1和DHEAS是轨迹分析的优秀候选：它们各自对应一个不同的激素通路；两者都对功能性衰老的关键生理系统有不同的影响（例如，心血管、肌肉骨骼和神经系统）；在人口水平上，两者都随着年龄的增长而减少。我们的中心假设是IGF-1和DHEAS的变化轨迹单独或共同预测老年人的健康、功能和生存。我们建议使用心血管健康研究（CHS）的数据来评估这一假设，这是一项已建立的、特征明确的、前瞻性的、由美国国立卫生研究院赞助的、针对65岁以上社区居住男性和女性的纵向研究。在16年的随访期间收集的现有数据，以及在这段时间内的8个时间点储存的血液标本，可用于拟议的分析。我们假设那些激素水平没有随时间下降的人会比那些整体下降的人以及激素水平随时间变化的人有更大的存活率和更高的功能水平。本研究提出以下研究目的：1)确定IGF-1和DHEAS的主要轨迹模式的流行程度，并确定每种轨迹模式与健康和生存的关系；2)确定男女之间轨迹模式的差异；3)确定单独基线值、单独独立轨迹值或独立轨迹加基线值是否是健康和生存的最佳预测指标；4)明确不良事件和运动对运动轨迹的影响；5)确定关节异常对IGF-1和DHEAS运动轨迹模式的影响。本研究是将内分泌稳态模型和轨迹分析应用于人口水平的衰老生物学研究的新方法。我们的工作将直接指导生长激素类似物和脱氢表雄酮的合适人群的选择。

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.