CANDIDATE BIOMARKERS OF AGING - AGE-SENSITIVE INDEXES OF IMMUNE AND MUSCLE FUNCTION COVARY IN GENETICALLY HETEROGENEOUS MICE

A longitudinal experiment was designed to test the hypothesis that ind ividual mice differ in their aging rate and to validate candidate biom arkers proposed to measure the rate of aging. Mice were bred as the ge netically heterogeneous progeny of a cross between CB6F1 mothers and C 3D2F1 father. Half of the mice were fed ad libitum (AL group), and the other half were subjected to 60% calorie restriction (CR group). Each mouse was tested at about 9 months of age using age-sensitive tests o f immune status, and then again at about 12 months of age using age-se nsitive tests of muscle function. The data were then analyzed using th e method of partial least squares to determine the combinations of tes t weights that maximize the covariance of the weighted sum of immune m easures with the weighted sum of muscle function measures. Both AL and CR mice exhibited a statistically significant relation between the im mune status tests and the muscle function tests. Maximal covariance wa s obtained with a set of weighting coefficients with our working hypot hesis: mice with high levels of CD4 memory T cells (which increase wit h age) also had relatively low levels of muscle strength and endurance . Low strength was associated with low CD8 cells in the AL mice, with high numbers of CD8 memory cells in the CR mice and with low CD3 cells in both diet groups. The partial least squares method generates compo site indices of immune status and muscle function that can be evaluate d as biomarkers of aging rate in these mice. Further work will be need ed to assess whether these tests predict either longevity or the traje ctory of change in other age-sensitive molecular and physiological tra its.