NEUROBEHAVIORAL AND IMMUNOLOGICAL MARKERS OF AGING

神经行为学、免疫学和分子变量是 被认为是衰老的潜在生物学标志。 长期 这些实验的目的是提供快速和 准确评估干预措施， 长寿，特别是那些旨在延长 多年的生活。 本提案的目标是确定 生物过程的有用标记物，其在功能上 与寿命相关（即，老化的生物标志物），从而允许更多 年龄的准确估计比时间的推移提供。 建议的实验将确定的有效性，通用性， 和C57 BL/6 NNia中19种潜在生物标志物的可重复性， DBA 2/6 NNia和B6 D2 F1小鼠，由NIA提供和饲养。 NCTR用于生物标志物研究。 学习行为测验 和记忆力，感觉和运动能力的测试，行为- 中枢神经功能的药理学探针， 神经化学变量、生理变量、免疫学变量 变量和异常蛋白质的细胞积累， 被提议作为衰老的潜在生物标志物。 的有效性 将在两个实验中测定生物标志物。 在一个 实验中，每种生物标志物对 断奶后开始的饮食限制（DR）将通过以下方式确定： 测试三个目标年龄的自由进食和DR小鼠， 他们的寿命。 预计有效的生物标志物应 区分已知寿命不同的小鼠组。 因为 众所周知，饮食限制具有延长寿命的作用， 预期有效生物标志物中与年龄相关的改变将 在DR小鼠中，相对于自由进食的小鼠， 在第二个实验中，潜在生物标志物的有效性 将被评估，以确定个人在多大程度上 生物标志物测量值的差异可预测 随后的寿命。 预计有效的生物标志物将是 与个体自由进食和DR的寿命相关 小鼠 每种生物标志物的一般性将通过以下方式确定： 比较两种不同基因型小鼠的结果， F1杂种。 每种生物标志物的重现性将 在每个实验的队列间重复中解决。 研究人员希望能提供几种有效的生物标志物， 根据当前RFA开发的整体面板。

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.