NEUROBEHAVIORAL AND IMMUNOLOGICAL MARKERS OF AGING

衰老的神经行为和免疫标志物

• 批准号: 3118906
• 负责人: HARBANS LAL
• 金额: $ 14.79万
• 依托单位: TEXAS COLLEGE OF OSTEOPATHIC MEDICINE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3118906
• 关键词: T lymphocyte; aging; amidation /deamidation; animal old age; behavior test; benzodiazepines; biomarker; body temperature regulation; dietary control; dopamine receptor; drug receptors; genetic strain; immunologic assay /test; laboratory mouse; learning; leukocyte activation /transformation; longevity; longitudinal animal study; mature animal; memory; neurochemistry; nicotinic receptors; nutrition of aging; nutrition related tag; physiology; psychomotor function; psychopharmacology; sensory mechanism; triose phosphate isomerase

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.

神经行为，免疫学和分子变量是 提出是衰老的潜在生物学标志物。 长期 这些实验提供的目标是提供快速和 准确评估可能影响的干预措施 寿命，尤其是那些旨在延长生产力的寿命 生活年。 该提议提供的目标是确定 在功能上的生物过程的有用标记 与长寿（即衰老的生物标志物）相关，从而允许更多 准确的年龄估计比时间的流逝所提供的。 提出的实验将确定有效性，一般性， 以及C57BL/6nnia中19个潜在生物标志物的可重复性， DBA2/6NNIA和B6D2F1小鼠，由NIA-提供和维护 NCTR用于生物标志物研究。 学习行为测试 以及记忆，感官和运动能力的测试，行为 - 中枢神经功能的药理探针， 神经化学变量，生理变量，免疫学 变量和异常蛋白质的细胞积累是 被提议为衰老的潜在生物标志物。 的有效性 生物标志物将在两个实验中确定。 一个 实验，每个生物标志物对 断奶后发起的饮食限制（DR）将由 在三个目标年龄段的三个目标年龄进行测试和DR小鼠 他们的寿命。 预计有效的生物标志物应该 区分已知的寿命不同的小鼠组。 因为 众所周知，饮食限制具有生命的影响，这是 期望有效的生物标志物中与年龄相关的变化将 相对于脂肪喂养的小鼠，在DR小鼠中减速。 在第二个实验中，潜在生物标志物的有效性 将评估确定个人的程度 生物标志物测量的差异是预测的 随后的寿命。 预计有效的生物标志物将会 与自由饲料和博士的单个寿命相关 老鼠。 每个生物标志物的一般性将由 比较两种不同小鼠基因型及其它们的结果 F1杂种。 每个生物标志物的可重复性将是 在每个实验的复制间复制中解决。 研究人员期望为几种有效的生物标志物贡献 为了响应当前的RFA而开发的整体面板。