QUANTITATIVE ANALYSIS OF AGING RATE PATTERNS

老化率模式的定量分析

• 批准号: 2704836
• 负责人: SHIRO HORIUCHI
• 金额: $ 17.98万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2704836
• 关键词: Invertebrata; age difference; aging; animal data; animal mortality; death; dietary constituent; disease /disorder proneness /risk; family genetics; gender difference; human data; human morbidity; human mortality; longitudinal human study; mathematical model; nutrition related tag; smoking; socioenvironment; species difference; statistics /biometry; tobacco abuse

DESCRIPTION: Mortality rises with age, reflecting the progression of physiological deterioration. The pattern of this age-related mortality increase may vary among causes of death, among species, between sexes, and among groups with different characteristics. These variations are important clues on the underlying mechanisms of senescence, evolutionary backgrounds of the mechanisms, relationships between senescence and diseases, and environmental and genetic effects on senescence. A statistical tool for examining the mortality trajectories is the LAR, which is the age-specific rate of relative mortality increase with age and is useful in detecting mortality accelerations and decelerations. Previous studies, however, did not analyze the differential age trajectories of mortality in depth. This is due to the prevalent view that the age patterns of mortality over a wide range of adult ages (except for very old ages) are similar for major degenerative causes of death and in many human and nonhuman populations, since they fit the exponential function fairly well. Thus those studies usually examined the average LAR (i.e., the Gompertzian aging rate) over age, but did not focus on age variations in the LAR. Serious limitations of this conventional approach have been revealed in some recent studies, which indicate significant age variations of the LAR not only at oldest ages but also at middle ages and younger old ages, and substantial differences in the LAR pattern between sexes, among diseases, and over time. In this project, the LAR analysis will be used for investigating (1) inter-species differentials in the age pattern of mortality and (2) environmental and genetic effects on the age pattern of mortality in humans and laboratory animals. In particular, the following assumptions and hypotheses will be tested: (a) the age-related mortality increase tends to slow down in earlier life stages in r-strategy (high fertility) species than in K-strategy (low mortality) species; (b) the mortality deceleration is more likely to be preceded by a phase of mortality acceleration in vertebrates than in invert-ebrates; (c) effects of factors that extend the lives of laboratory animals differ with respect to four major dimensions (initial mortality, oldest-old mortality, pace of senescence, and timing of senescence); (d) risk factors involved in the accumulation of free radical damages in humans (e.g., smoking and diet) affect the rate of age-associated mortality increase; and (e) the diffusion of smoking has altered the age pattern of male mortality consid-erably. A new multivariate method, called the power-function hazard model analysis, will be developed for analyzing effects of risk factors on aging rates.

描述：死亡率随着年龄的增长而上升，反映了疾病的进展 生理恶化。 这种与年龄相关的死亡率的模式 增加可能因死亡原因、物种、性别和性别而异 具有不同特征的群体之间。 这些变化很重要 关于衰老的潜在机制、进化背景的线索 衰老与疾病之间的机制、关系，以及 环境和遗传对衰老的影响。 一个统计工具 检查死亡率轨迹的是 LAR，它是年龄特定的 相对死亡率随着年龄的增长而增加，有助于检测 死亡率加速和减速。 然而，之前的研究并未分析差异年龄轨迹 深度的死亡率。 这是因为人们普遍认为年龄 不同成年人年龄范围内的死亡率模式（高龄老人除外） 年龄）对于主要的退行性死亡原因是相似的，并且在许多人类中 和非人类群体，因为它们相当符合指数函数 出色地。 因此，这些研究通常检查平均 LAR（即 冈珀兹老化率）超过了年龄，但没有关注年龄的变化 拉尔。 这种传统方法的严重局限性已经暴露出来 最近的一些研究表明，LAR 的年龄存在显着差异 不仅在老年，而且在中年和年轻的老年， 不同性别、不同疾病之间的 LAR 模式存在显着差异， 随着时间的推移。 在本项目中，LAR 分析将用于调查 (1) 死亡率年龄模式的物种间差异以及 (2) 环境和遗传对人类死亡率年龄模式的影响 和实验动物。 特别是，以下假设和 将检验以下假设： (a) 与年龄相关的死亡率增加趋向于 r策略（高生育力）物种在早期生命阶段的速度比 K-策略（低死亡率）物种； (b) 死亡率减速为 在此之前更有可能出现死亡率加速上升的阶段 脊椎动物多于无脊椎动物； (c) 延长期限的因素的影响 实验动物的生活在四个主要方面存在差异 （初始死亡率、最年老死亡率、衰老速度和衰老时间 衰老）; (d) 自由基积累的危险因素 人类的损害（例如吸烟和饮食）会影响与年龄相关的发病率 死亡率增加； (e) 吸烟的扩散改变了年龄 男性死亡率的模式相当明显。 一种新的多元方法，称为 幂函数风险模型分析将被开发用于分析 风险因素对老龄化率的影响。