Assessing the predictive validity of psychomotor tests as measures of biological age in mice

Abstract

Two experiments assessed the predictive validity of a psychomotor test battery in male C57BL/6J mice. First, performance was recorded for 66 mice in rotorod, tightrope, grip strength, exploratory activity, and runwheel activity tasks at 24 mo of age. Except in the rotorod task, performance was positively and significantly correlated to lifespan, i.e. better performance indicated longer lifespan. Body weight and body temperature were also significantly correlated with lifespan, while water consumption was negatively related. Using the five behavioral scores in a multiple regression analysis, about 40% of the variance in lifespan was explainable. When measures of body weight, body temperature, and water consumption were added to the regression equation, about 54% of the variance in lifespan could be explained. As revealed by factor analysis, a high degree of interrelationship existed among variables. In a second experiment, 54 mice were tested in the psychomotor battery every 8 weeks from 24 mo. Scores in the tightrope and both locomotor activity tasks revealed age-related declines, whether considering all individuals or only those surviving to 28 mo. Significant correlations between first and subsequent scores indicated stability of individual differences for tightrope and exploratory activity at most ages and for runwheel activity at 26 mo but not later. Rotorod and grip strength scores were not stable and suggested confounding by learning. Significant correlations with lifespan were obtained at some ages for all tests. In contrast to the first experiment, however, there were no significant correlations between lifespan and scores at 24-mo for any test and little correlation among scores. The results demonstrate how the predictive validity of behavioral tests can be assessed but suggest that further refinement of this battery is necessary.