Hormonal trajectories in aging

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，因此在维持体内平衡的恢复力中也起着关键作用。虽然 很明显，在群体水平上，许多激素随着年龄的增长而下降，对个体的分析表明， 从未进行过涉及多个时间点的轨迹。因此，预测的问题 个别轨迹的价值仍然没有答案。IGF-1和DHEAS代表了 轨迹分析：每一个对应于一个不同的激素途径;两者都有不同的影响 对于功能老化至关重要的生理系统（例如，心血管、肌肉骨骼和神经系统）;以及 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的变化轨迹 和DHEAS单独和联合预测老年人的健康，功能和生存。我们建议评估 这一假设使用了来自心血管健康研究（CHS）的数据，该研究是一项已建立的，特征良好的， 前瞻性，NIH赞助的65岁以上社区居民男性和女性的纵向研究。 在16年随访期内收集的现有数据，包括8个时间点的库存血液标本 在这段时间内，可用于拟议的分析。我们假设那些没有下降的人 随着时间的推移，他们的荷尔蒙水平将有更大的生存和保留更高水平的功能与老化 而不是那些轨迹表现出整体下降的人，以及那些在 荷尔蒙水平随时间变化本研究提出以下研究目的：1）界定 IGF-1和DHEAS的主要轨迹模式，并确定每一个的关联 轨迹模式与健康和生存，2）以确定男性和女性之间的差异， 轨迹模式，3）确定是否单独使用基线值、单独使用独立轨迹，或 独立轨迹加上基线值是健康和生存的最佳预测因子，4） 明确不良事件和运动对轨迹的影响，5）确定关节运动的影响 IGF-1和DHEAS的轨迹模式异常。本研究是内分泌免疫学的一个新应用， 稳态模型和轨迹分析，以研究人口水平上的老龄化生物学。我们 这项工作将直接指导生长激素类似物和脱氢表雄酮的适当人群的选择。

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 inIGF-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-1and 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.