QUANTITATIVE ANALYSIS OF AGING RATE PATTERNS

老化率模式的定量分析

• 批准号: 6043083
• 负责人: SHIRO HORIUCHI
• 金额: $ 18.52万
• 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 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6043083
• 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 生理退化 这种与年龄相关的死亡率模式 死亡原因、物种、性别之间的增加可能有所不同， 在不同特征的群体中。 这些变化很重要 衰老的潜在机制、进化背景 衰老和疾病之间的机制和关系， 环境和遗传对衰老的影响。 统计工具， 检查死亡率轨迹的是LAR，这是特定年龄的 相对死亡率随着年龄的增长而增加， 死亡率的加速和减速。 然而，以前的研究没有分析不同的年龄轨迹， 死亡的深度。 这是由于普遍认为，年龄 成年人年龄范围很广的死亡率模式（非常老的除外） 年龄）是相似的主要退化性死亡原因，在许多人 和非人类群体，因为他们符合指数函数 好. 因此，这些研究通常检查平均LAR（即，的 Gompertzian老化率），但没有关注年龄的变化， LAR。 这种传统方法的严重局限性已经被揭示出来 在最近的一些研究中，表明LAR的年龄差异很大， 不仅在最老的年龄，而且在中年和更年轻的老年， 不同性别、不同疾病、 随着时间的推移。 在本项目中，LAR分析将用于调查（1） 死亡率年龄模式的种间差异和（2） 环境和遗传对人类死亡年龄模式的影响 实验室动物 具体而言，以下假设和 将检验以下假设：（a）与年龄有关的死亡率增加的趋势是： 在r-策略（高生育力）物种的早期生命阶段比 在K-策略（低死亡率）物种中;（B）死亡率减速是 更有可能在死亡加速阶段之前， （c）在无脊椎动物中， 实验室动物的生活在四个主要方面不同， （初始死亡率、最年长者死亡率、衰老速度和衰老时间） （d）与自由基积累有关的风险因素 对人体的损害（例如，吸烟和饮食）影响与年龄相关的 死亡率增加;（e）吸烟的扩散改变了年龄 男性死亡率的模式 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 风险因素对衰老率的影响。