Biomarkers of aging: Prediction of longevity by using age-sensitive T-cellsubset determinations in a middle-aged, genetically heterogeneous mouse population

Seven T-cell subset values were measured in each of 559 mice at 8 months of age, and then again in the 494 animals that reached 18 months of age. The group included virgin males, virgin females, and mated females, and it was produced by using a four-way cross-breeding system that generates genetic h eterogeneity equipment to a very large sibship. An analysis of covariance s howed that four T-cell subsets-CD4 CD4 memory, CD4 naive, and CD4 cells exp ressing P-glycoprotein-were significant predictors (p < .003) of longevity when measured at 18 months of age after adjustment for the possible effects of gender and mating. The subset marked by CD4 and P-glycoprotein expressi on showed a significant interaction effect: this subset predicted longevity only in males. Among subsets measured when the mice were 8 months of age, only the levels of CD8 memory cells predicted longevity (p = .016); the pro gnostic value of this subset was largely limited to mated females. A cluste r analysis that separated mice into two groups based upon similarity of T-c ell subset patterns measured at IX months showed that these two groups diff ered in life expectancy. Specifically, mice characterized by relatively low levels of CD4 and CD8 memory cells, high levels of CD4 naive cells, and lo w levels of CD4 cells with P-glycoprotein (64% of the total) lived signific antly longer (50 days = 6%; p < .0007) than mice in the other cluster. The results are consistent with the hypothesis that patterns of T-cell subsets vary among mice in a manner than can predict longevity in middle age, and t hey suggest that these subsets may prove to be useful for further studies o f the genetics of aging and age-sensitive traits.