Prolonged Lifespan, Ameliorated Cognition, and Improved Host Defense of Caenorhabditis elegans by Lactococcus lactis subsp. cremoris

This study evaluated whether the lactic acid bacteria Lactococcus lactis subsp. cremoris strain FC (FC) could ameliorate host defenses and cognitive ability and extend the lifespan of Caenorhabditis elegans, a model of senescence. The lifespan and resistance to physical, chemical, and biological stressors were compared between C. elegans fed FC and those fed Escherichia coli OP50 (OP), an international standard food for C. elegans. Living FC successfully extended the health span, enhanced host defense, and ameliorated the cognitive ability of the nematodes; even the exopolysaccharides (EPSes) of FC could extend the lifespan of C. elegans. The chemotaxis index, which was used to evaluate the senescence of sensory neurons, tended to decrease with aging; however, it was more stable in worms fed FC and was significantly higher than that of the control worms at 7 days of age. The worms fed FC were tolerant to Salmonella enterica serovar Enteritidis or Staphylococcus aureus infection and had better survival than the control worms fed OP. FC showed beneficial effects in C. elegans daf-16 and pmk-1 mutants, but not in skn-1 mutants. Since SKN-1 is the C. elegans ortholog of Nrf2, we measured the transcription of heme oxygenase-1 (HO-1), which is regulated by Nrf2, in murine macrophages and found that HO-1 mRNA expression was increased >5 times by inoculation with either FC cells or heat-killed bacteria with EPSes. Thus, both FC and the EPSes can affect longevity via the SKN-1/Nrf2 pathway in both nematodes and mammalian cells. IMPORTANCEAgeing is one of our greatest challenges. The World Health Organization proposed the concept of "Active Ageing" might encourage people to continue to work according to their capacities and preferences as they grow old and would prevent or delay disabilities and chronic diseases that are costly to both individuals and the society, considering that disease prevention is more economical than treatment. Probiotic bacteria such as lactobacilli are living microorganisms that exert beneficial effects on human health when ingested in sufficient amounts and can promote longevity. The significance of this study is that it revealed the anti-senescence and various beneficial effects of the probiotic representative bacterium Lactococcus lactis subsp. cremoris strain FC and its exopolysaccharides in the nematode Caenorhabditis elegans.