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.
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