Common mucosal immune responses were depressed in aged mice that were orally immunized with Haemophilus influenzae type b oligosaccharide conjugated to Diphtheria CRM197 protein (Hib-DT) vaccine using cholera toxin as the mucosal adjuvant. Both common mucosal and systemic humoral immune responses were also depressed in aged mice that were subcutaneously immunized with vaccine formulations containing Hib-DT plus 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Dietary supplementation of aged mice with either the antioxidant vitamin E, or with known activators of the alpha isoform of the peroxisome proliferator activated receptor (PPAR-alpha) was capable of restoring their mucosal and systemic humoral immune responses to mature adult levels, by both the oral and subcutaneous routes of immunization. These data support a hypothesis that some aspects of immunosenescence are due to dysregulations in cellular functions, and are not due to any irreversible defects in cellular components of the immune system.