NEUROBEHAVIORAL AND IMMUNOLOGICAL MARKERS OF AGING

神经行为、免疫学和分子变量是 被认为是潜在的衰老生物标志物。长期的 这些实验的目的是提供快速和 准确评估可能影响的干预措施 长寿，特别是那些旨在延长生产力的长寿 生命中的岁月。这项提案的目标将是确定 生物过程的有用标记，其功能是 与长寿有关(即，衰老的生物标志物)，因此允许更多 对年龄的准确估计比时间的流逝提供的更准确。 拟议的实验将确定有效性、一般性、 和19个潜在生物标志物在C57BL/6NNia中的重复性， DBA2/6NNia和B6D2F1小鼠，由NIA提供和维护- NCTR用于生物标记物研究。学习的行为测试 以及记忆力，感觉和运动能力测试，行为测试- 中枢神经功能的药理探针， 神经化学变量、生理变量、免疫学 变量和细胞内异常蛋白的积累是 被认为是潜在的衰老生物标志物。法律程序的有效性 生物标志物将在两个实验中确定。合而为一 实验中，每个生物标志物对影响的敏感性 断奶后启动的饮食限制(DR)将由以下因素确定 在三个目标年龄段测试自由喂养和DR小鼠 他们的寿命。预计有效的生物标志物应该 区分已知寿命不同的小鼠组。因为 节食有延年益寿的作用，这是众所周知的 预计有效生物标志物中与年龄相关的变化将 在DR小鼠中，相对于随意喂养的小鼠，其运动速度减慢。 在第二个实验中，潜在生物标记物的有效性 将被评估为确定个人在多大程度上 生物标志物测量的差异可以预测 随后的寿命。预计有效的生物标志物将是 与个体随机喂养和DR的寿命相关 老鼠。每个生物标志物的一般性将由以下因素决定 比较两种不同的小鼠基因和它们的结果 F1混合动力车。每个生物标志物的重复性将是 在每个实验的队列间重复中解决。 研究人员预计将贡献几个有效的生物标志物来 将针对当前的RFA开发的整体小组。

Neurobehavioral, immunological, and molecular variables are proposed as potential biological markers of aging. The long-term objectives served by these experiments is to provide rapid and accurate assessment of interventions which could affect longevity, particularly those aimed at prolonging the productive years of life. The goal served by this proposal will be to identify useful markers of biological processes which are functionally linked to longevity (i.e., biomarkers of aging), thus allowing more accurate estimation of age than provided by the passage of time. The proposed experiments will determine the validity, generality, and reproducibility of 19 potential biomarkers in C57BL/6NNia, DBA2/6NNia, and B6D2F1 mice, provided and maintained by NIA- NCTR for the biomarker research. Behavioral tests of learning and memory, tests of sensory and motor abilities, behavioral- pharmacological probes of central nervous function, neurochemical variables, physiological variables, immunological variables, and cellular accumulation of abnormal proteins are proposed as potential biomarkers of aging. The validity of the biomarkers will be determined in two experiments. In one experiment, the sensitivity of each biomarker to the effects of postweaning-initiated diet restriction (DR) will be determined by testing ad libitum fed and DR mice at three target ages across their lifespans. It is expected that valid biomarkers should differentiate groups of mice known to differ in life span. Because diet restriction is known to have life-prolonging effects, it is expected that age-related alterations in the valid biomarkers will be decelerated in the DR mice, relative to ad-libitum fed mice. In a second experiment, the validity of the potential biomarkers will be assessed be determining the extent to which individual differences in the biomarker measurements are predictive of subsequent lifespan. It is expected that valid biomarkers will be correlated with longevity in individual ad libitum fed and DR mice. The generality of each biomarker will determined by comparing results across two divergent mouse genotypes and their F1 hybrids. The reproducibility of each biomarker will be addressed in a between-cohort replication of each experiment. The researchers expect to contribute several valid biomarkers to the overall panel to be developed in response to the current RFA.