The present study was conducted to test the ability of probiotic lactobacilli to alter age-related immunosenescence in host animals. Senescence-accelerated mouse prone 1 mice were orally fed heat-killed Lactobacillus gasseriTMC0356 (TMC0356) for 4 and 8 weeks at dosages of 10 mg day−1 after a 16-week period of prefeeding with a standard diet. After 4 and 8 weeks of TMC0356 intervention, splenic activation of natural killer (NK) cells and mRNA expression of cytokines and other immune molecules in the lungs were analysed. After 4 and 8 weeks, splenic NK cell activities were significantly higher in the TMC0356-fed mice compared with control mice (P < 0.05). After 4 weeks, mRNA expression of interleukin-2 and interferon-(α and β) receptor 1 in lung cells isolated from the TMC0356-fed mice also increased significantly compared with that in lung cells from the control mice (P < 0.05). These results suggest that lactobacilli, especially certain selected strains, might enhance cell-mediated immunity in host animals and thereby alter age-related immunosenescence.