Lifelong treatment with oral DHEA sulfate does not preserve immune function, prevent disease, or improve survival in genetically heterogeneous mice.

To determine whether lifelong exposure to dehydroepiandrosterone sulfate extends the lifespan or retards immune senescence in mice. Double-blind, placebo-controlled intervention trial. A specific pathogen-free rodent vivarium. 120 mice bred as a cross between CB6F1 females and C3D2F1 males. DHEAS at 100 microg/mL in drinking water from weaning until death. Age at death, cause of death, antibody production after erythrocyte immunization, and T cell subset profiles in peripheral blood at ages 8 and 18 months. DHEAS ingestion did not lead to a significant increase in mean or maximal longevity: the 95% confidence interval for DHEAS effect on mean lifespan ranged from +35 days to -80 days. There were no significant effects of DHEAS on incidence of lethal illnesses, except for a trend toward higher levels of mammary adenocarcinoma in DHEAS-treated females and mouse urinary syndrome in DHEAS-treated males. DHEAS treatment did not improve the ability of middle-aged mice to produce antibody to a foreign particulate antigen, and it did not alter the proportions of age-sensitive T cell subsets in middle-aged animals. Although differences among species in pharmacokinetics complicate interpretation of studies in which DHEA or DHEAS is administered to rodents, our data provide no support for the idea that chronic exposure to this steroid retards immune senescence or prevents late life illness.