MORTALITY AND BIOMARKERS OF AGING IN HETEROGENEOUS STOCK (HS) MICE

A longitudinal study was undertaken to evaluate the relationships amon g a battery of aging biomarkers and subsequent survival time in 319 ge netically heterogenous stock (HS) mice. The biomarker variables chosen were selected from the broad domains of behavior, homeostatic physiol ogy, oxidative defense, and immune function; biomarkers were measured at 45, 90, 360, 630, and 900 days of age. Sex differences were found i n the survivor and mortality functions, with a mortality rate crossove r occurring at about 525 days and a survival curve crossover at about 750 days of age. Females experienced lower initial mortality but had m ore sharply increasing mortality with age than did males. Survival ana lysis using Gompertz parametric models with biomarkers as time-varying covariates yielded significant biomarkers from each domain. Following backward elimination procedures, the final set of independent mortali ty predictors included headpokes in the File activity apparatus, maxim um card drop time, weight, hematocrit, urine concentration, natural ki ller cell activity, and concanavalin A response.