Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 53, Issue 3 B217-B230, Copyright © 1998 by The Gerontological Society of America
Mortality and biomarkers of aging in heterogeneous stock (HS) mice
DA Heller, FM Ahern, JT Stout and GE McClearn
Department of Biobehavioral Health, Pennsylvania State University, USA.
A longitudinal study was undertaken to evaluate the relationships among a
battery of aging biomarkers and subsequent survival time in 319 genetically
heterogenous stock (HS) mice. The biomarker variables chosen were selected
from the broad domains of behavior, homeostatic physiology, oxidative
defense, and immune function; biomarkers were measured at 45, 90, 360, 630,
and 900 days of age. Sex differences were found in the survivor and
mortality functions, with a mortality rate crossover occurring at about 525
days and a survival curve crossover at about 750 days of age. Females
experienced lower initial mortality but had more sharply increasing
mortality with age than did males. Survival analysis 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 mortality predictors included
headpokes in the File activity apparatus, maximum cord drop time, weight,
hematocrit, urine concentration, natural killer cell activity, and
concanavalin A response.
