DYNAMIC DETERMINANTS OF EXCEPTIONAL HEALTH AT LATE AGES

描述(由申请人提供)：拟议研究的广泛长期目标是通过结合在不同纵向研究中收集的数据，评估生理指标的年龄轨迹以及其他因素作为老年人异常健康的决定因素的作用。具体目的：1.采用传统统计学方法，评价所选各项生理指标的年龄轨迹以及在Framingham心脏研究(FHS)、Framingham子孙研究(FHSO)和火奴鲁鲁心脏研究(HHS)中测量的其他因素对老年人异常健康的影响。评估风险因素的影响随年龄的变化。2.建立数学和计算机模型，描述每个生理指标的年龄动态产生机制，包括它们的动态平衡调节的可能性和与健康结果的动态联系。使用这些模型分析FHS、HHS和FHSO数据，以：a)评估每个选定生理指标中与年龄相关的动态平衡调节系数随年龄的变化及其在健康老龄化中的作用；b)评估每个指标在决定健康结果方面随年龄的变化。3.评估决定一组选定生理指标的关节动力学的特征随年龄的变化，以及这些指标对健康结果的影响的变化。评估“正常”或“最佳”生理状态的年龄轨迹及其可容忍的偏差范围。为此，开发描述一组生理指标的关节年龄动态及其与健康结果的关系的数学和计算机模型。在FHS、FHSO和HHS数据分析中使用该模型来解决上述问题。4.在FHS、FHSO和HHS数据的联合分析中，评估老年异常健康的动态决定因素。为此，针对三个选定的数据集中的每一个，开发描述一组选定的生理指数的关节动力学及其与健康结果的关系的兼容的数学和计算机模型，并在这三个纵向数据集的联合分析中使用这些模型。评估参与联合数据分析的人群中老年异常健康的动态决定因素的差异和相似之处。在FHS和FHSO数据的联合分析中，评估遗传和非遗传因素对晚年异常健康的贡献。

DESCRIPTION (provided by applicant): The broad long-term objectives of the proposed research are evaluation of the role of age trajectories of physiological indices as well as other factors as determinants of exceptional health among the elderly, by combining data collected in different longitudinal studies. Specific aims: 1. Evaluate effects of age trajectories of each of the selected physiological indices, as well as other factors measured in Framingham Heart Study (FHS), Framingham Offspring Study (FHSO) and Honolulu Heart Study (HHS), on exceptional health among the elderly using traditional statistical methods. Evaluate changes in the effects of risk factors with age. 2. Develop mathematical and computer models describing mechanisms generating age dynamics of each physiological index including possibility of their homeostatic regulation and dynamic connection to health outcomes. Use these models in the analysis of FHS, HHS and FHSO data to: a) evaluate age related changes in coefficients of homeostatic regulation with age in each of selected physiological indices and their role in healthy aging; b) evaluate changes in the role of each index in determining health outcomes with age. 3. Evaluate age-related changes in characteristics determining joint dynamics of a set of selected physiological indices, as well as changes in effects of these indices on health outcomes. Evaluate age trajectories of "normal" or "optimal" physiological state as well as the range of tolerable deviations from it. For this purpose develop mathematical and computer model describing joint age dynamics of a set of physiological indices and its connection to health outcomes. Use this model in the analysis of FHS, FHSO and HHS data to address issues formulated above. 4. Evaluate dynamic determinants of exceptional health at late ages in the joint analysis of FHS, FHSO and HHS data. For this purpose develop compatible mathematical and computer models describing joint dynamics of a set of selected physiological indices and their connection to health outcomes for each of three selected data sets and use these models in joint analysis of these three longitudinal data sets. Evaluate differences and similarities in dynamic determinants of exceptional health at late ages in populations participating in joint analysis of data. Evaluate contribution of genetic and non-genetic factors in exceptional health at late ages in the joint analysis of FHS and FHSO data.