Hormonal trajectories in aging

新陈代谢调节对于体内平衡和面对外部威胁的韧性至关重要。荷尔蒙 在新陈代谢调节中发挥关键作用，因此，在维持体内平衡弹性方面发挥关键作用。尽管它是 很明显，在种群水平上，许多激素随着年龄的增长而下降，对个体的分析 涉及多个时间点的轨迹从未被执行过。因此，预测性的问题 个人轨迹的价值仍未得到回答。IGF-1和DHEAS是优秀的候选者 轨迹分析：每一种都对应着不同的荷尔蒙途径；两者对 对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 在人口层面上，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单独和联合预测健康、功能和老年生存。我们建议评估 这一假设使用了心血管健康研究(CHS)的数据，这是一项成熟的、特征良好的、 由美国国立卫生研究院赞助的对65岁以上社区居住的男性和女性进行的前瞻性纵向研究。 在16年的随访期内收集的现有数据，在8个时间点保存了血液样本 在这段时间内，可以用于建议的分析。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会有更大的存活率，并随着年龄的增长保持更高的功能水平 比那些轨迹显示总体下降的人和那些在 超时的荷尔蒙水平。本研究提出以下研究目标：1)界定儿童精神分裂症患病率 IGF-1和DHEAS的主要轨迹模式及其相互关系 轨迹模式与健康和生存的关系，2)确定男性和女性在 轨迹模式，3)建立单独的基线值、单独的独立轨迹或 独立轨迹加上基准值是健康和生存的最佳预测因子，4) 定义不良事件和运动对运动轨迹的影响，以及5)确定关节的影响 IGF-1和DHEAS的轨迹模式异常。这项研究是内分泌的一个新的应用 在人口层面研究老龄化生物学的动态平衡模型和轨迹分析。我们的 这项工作将直接指导为生长激素类似物和脱氢表雄酮选择合适的人群。

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.