SERUM ALBUMIN AS BIOMARKER OF AGING IN CAPTIVE RHESUS MONKEYS
D. A. Smucny*1, D. B. Allison3, D. K. Ingram2, E. Nakamura4, J. Herndon5, J.W. Kemnitz1, G. S. Roth2, M. A. Lane2
*1Wisconsin Regional Primate Research Center, 1220 Capitol Court, Madison, WI 53715; 2 Laboratory of Neurosciences, National Institute on Aging, NIH, Baltimore, MD; 3Department of Biostatistics and Center for Research on Clinical Nutrition, University of Alabama at Birmingham, Birmingham, AL;4Division of Natural Environmental Sciences, Kyoto University, Japan; 5Yerkes Regional Primate Research Center, Emory University, Atlanta, GA.
Biomarkers of aging can provide useful tools for predicting functional capability in later life, and for assessing the effectiveness of an intervention or treatment on the rate of aging processes. However, no consensus has been developed regarding methods for identifying and validating candidate biomarkers of aging. In the current study, we offer a strategy for validating serum albumin as candidate biomarker of aging in rhesus monkeys. Using a large multi-centered Primate Aging Database (PAD), containing longitudinal and cross-sectional data for a number of primate species, we investigated whether serum albumin obtained from rhesus monkeys: (1) showed a significant negative cross-sectional correlation with age; (2) showed significant negative longitudinal change; (3) demonstrated significant stability of differences over time. Using comparative PAD data for 7 different primate species, we also examined whether (4) rate of change in serum albumin during adulthood correlated to differences in species maximum lifespan. PAD provides a unique research resource in that it includes a wide distribution of ages across species, with a primary focus on adult and aged (i.e., post-maturational) animals. To test cross-sectional effects, longitudinal effects and stability of albumin measurements with age, we used a sample of 2000+ data points for serum albumin (g/dL) obtained from a large sample of apparently normal, healthy, non-experimental rhesus subjects (Macaca mulatta) over a 13-year period (1987-1999). Statistical analyses of these data included simple linear regression, multiple regression, and random regression modeling combined with multiple imputation. To assess albumin stability over time, we calculated a stability statistic to compare the adjacent yearly residuals from least squares regressions. To test the relationship of serum albumin slope with maximum lifespan in the comparative data, we calculated the correlation coefficient between maximum lifespan values and rate of change in albumin with age. Results confirmed that serum albumin met our four proposed criteria for a biomarker of aging. For our comparative sample, there was a significant correlation of the albumin slope (with age in adulthood) with maximum lifespan values, suggesting that shorter-lived species showed a more rapid rate of decline in albumin. Our results support the validity of serum albumin as a biomarker of aging for rhesus monkeys. Rhesus monkeys are the nonhuman primate model most commonly employed in aging studies. Therefore, a practical and readily accessible biomarker of aging (such as serum albumin) could prove useful for aging research.
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