STATISTICAL ANALYSIS OF BIOMARKERS OF AGING

衰老生物标志物的统计分析

• 批准号: 3123023
• 负责人: FRED LEON BOOKSTEIN
• 金额: $ 13.68万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-15 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3123023
• 关键词: Rodentias; aging; biomarker; computer program /software; data collection; dietary control; genotype; longevity; longitudinal animal study; nutrition related tag; statistics /biometry; technology /technique development

This proposal responds to Part B, "Statistical Analysis of Biomarkers of Aging," of RFA AG-91-17, "Development of Biomarkers of Aging." Since 1988, several investigators in the NIA Biomarkers Initiative have been gathering biometric and psychometric data comparing diverse aspects of structure and function between rodents fed ad libitum and dietary-restricted animals. Collection of such data will continue over the period for which the present funding is requested. There result many megabytes of data representing a great diversity of aspects of biological structure and function measured in many different channels and on various schedules (longitudinally, at death, at sacrifice at fixed ages) in seven distinct genotypes for each sex. From this variety of experimental designs and measurements we propose to extract and calibrate assessments of gerontological age, or biomarkers, in a form suggesting generalizations to other species and to humans. The operationalization of "biomarker" proposed for this project is a quasilinear composite, a weighted sum of smoothly transformed versions of raw measurements that covaries with a "composite time" in a statistically optimal way. Composite time is a weighted contrast of time-since-birth with time-until-death, corresponding to the two criteria typically used to characterize biomarkers in the literature. Whenever the available data comprise a truly longitudinal design, these composites can be computed and validated, and various important gerontometric hypotheses calibrated or tested with their aid. These include the relative salience of each measurement included in the biomarker panels, the extent to which it leads or lags other members of the panel, the extent to which it discriminates the two dietary groups, the extent to which its sensitivity to gerontological age is shared between genotypes , and similar questions. These composite scores will be computed by the method of nonlinear Partial Least Squares. Composite biomarkers that emerge from the analysis of longitudinal data can be used to calibrate similar series of age-specific means emerging from the cross-sectional designs. The collection of potential biomarkers that results will be ordered along a few distinct dimensions of functional or gerontological age and will be assessed by both power to predict longevity and sensitivity to dietary restriction. Their synthesis into panels for future testing in primates and humans speaks directly to the overall programmatic intent of the Biomarkers Initiative.

该提案对B部分做出了回应：“对生物标志物的统计分析 衰老，“ RFA AG-91-17”，衰老的生物标志物的发展。” 1988年，NIA生物标志物倡议的几位调查员已经 收集生物识别和心理测量数据，比较 啮齿动物的结构和功能 饮食限制动物。 此类数据的收集将继续 要求目前的资金的期限。 结果很多 大量数据代表了生物学的各个方面 结构和功能在许多不同的渠道和各种渠道中衡量 时间表（在固定年龄纵向，死于牺牲时，死于牺牲时） 每种性别的独特基因型。 从这些各种实验设计和测量中，我们提出 提取和校准评估老年学年或生物标志物的评估 以暗示对其他物种和人类进行概括的形式。 这 为该项目提出的“生物标志物”的操作是一个 准线性复合材料，平稳转化版本的加权总和 在统计上与“复合时间”协变的原始测量 最佳方式。 综合时间是时间 - 时间的加权对比度 与时间直到死亡，对应于通常使用的两个标准 描述文献中的生物标志物。 每当可用时 数据包括真正的纵向设计，这些复合材料可以是 经过计算和验证，以及各种重要的老年测量假设 用他们的帮助进行校准或测试。 这些包括相对显着性 生物标志物面板中包括的每个测量 它领导或滞后小组的其他成员 区分两个饮食组，其灵敏度的程度 在基因型和类似的基因型之间共享老年学年年龄 问题。 这些综合分数将通过 非线性部分最小二乘。 从纵向数据分析中出现的复合生物标志物 可以用来校准类似的一系列年龄特异性手段 来自横截面设计。 潜在生物标志物的收集 该结果将沿着几个不同的维度订购 功能或老年龄年龄，将通过两种能力评估 预测寿命和对饮食限制的敏感性。 他们的 合成在灵长类动物和人类中的未来测试的面板中 直接达到生物标志物计划的总体程序意图。