Tomomi Komura

Abstract Lactic acid bacteria (LAB) contribute to human health, and LAB functionality has been studied using Caenorhabditis elegans as an alternative host. However, many studies have focused on the efficacy of a single strain of LAB, and few reports have compared various LAB strains. In this study, we examined the effects of 15 strains of LAB isolated from vegetables, meat, and fermented foods on nematode longevity and healthy lifespan. To reduce the frequency of laborious survival observations, we performed a lifespan assay on agar plates containing 2′-deoxy-5-fluorouridine (FUdR), which inhibits egg-hatching and prevents generation mixing. Four beneficial strains showed significant lifespan extension and increased spontaneous nematode mobility, regardless of treatment with or without FUdR and the frequency of survival observation. These results suggested increased longevity and an extended healthy lifespan, which confirming the reliability of our method. The four strains are expected to show anti-ageing effects besides longevity and have effects on age-related degenerative diseases. Our labour-saving method can be used as an alternative to conventional methods and enable simultaneous screening of multiple strains. Future research could explore factors contributing to lifespan regulation by comparing and verifying differential strain effects on lifespan.

Lactic acid bacteria are beneficial to Caenorhabditis elegans; however, bacteria acting as probiotics in nematodes may not necessarily have probiotic functions in humans. Lactococcus cremoris subsp. cremoris reportedly has probiotic functions in humans. Therefore, we determined whether the strain FC could exert probiotic effects in C. elegans in terms of improving host defenses and extending life span. Live FC successfully extended the life span and enhanced host defense compared to Escherichia coli OP50 (OP50), a standard food source for C. elegans. The FC-fed worms were tolerant to Salmonella enterica subsp. enterica serovar Enteritidis or Staphylococcus aureus infection and had better survival than the OP50-fed control worms. Further, the chemotaxis index, an indicator of perception ability, was more stable and significantly higher in FC-fed worms than in the control worms. The increase in autofluorescence from advanced glycation end products (AGEs) with aging was also ameliorated in FC-fed worms. FC showed beneficial effects in 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 FC cells. Thus, FC could exert antisenescence effects via the SKN-1/Nrf2 pathway. This study showed for the first time that FC supported perceptive function and suppressed AGEs in nematodes as probiotic bacteria. Therefore, C. elegans can be an alternative model to screen for probiotic bacteria that can be used for antisenescence effects in humans. IMPORTANCE Aging is one of our greatest challenges. The World Health Organization proposed that "active aging" 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 live 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 antisenescence and various beneficial effects of the representative probiotic bacterium Lactococcus cremoris subsp. cremoris strain FC exerted via the SKN-1/Nrf2 pathway in the nematode Caenorhabditis elegans.Aging is one of our greatest challenges. The World Health Organization proposed that "active aging" 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.

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