The Transcription Factor DAF-16 is Essential for Increased Longevity in C. elegans Exposed to Bifidobacterium longum BB68

Abstract

The longevity-promoting benefits of lactobacilli were hypothesized as early as 1907. Although the anti-aging effects of lactic acid bacteria (LAB) have been observed in nematodes, rodents and humans for over a century, the mechanisms underlying the effects of probiotics on aging have rarely been assessed. Using the Caenorhabditis elegans (C. elegans) model, various studies have elucidated the role of different signaling cascades, especially the DAF-16 cascade, on lifespan extension by LAB. In this study, the mechanisms through which Bifidobacterium longum strain BB68 affects the longevity of C. elegans were assessed. The lifespan of nematodes increased by 28% after worms were fed BB68, and this extension of lifespan was completely lost in backgrounds containing a mutated DAF-16 gene. High levels of DAF-16 (in the daf-16 (mu86); muIs61 strain) nuclear accumulation and high expression of the SOD-3 gene (a DAF-16-specific target gene) were observed as a result of BB68 treatment. Immunofluorescence microscopy revealed that TIR-1 and JNK-1 are involved in the phosphorylation and activation of DAF-16. Thus, BB68 increased the longevity of nematodes by activating the TIR-1 – JNK-1 – DAF-16 signaling pathway, and the cell wall component of BB68 contributed to longevity.

A Combined Proteomics, Metabolomics and In Vivo Analysis Approach for the Characterization of Probiotics in Large-Scale Production

“…This finding is not surprising since it has been reported that other probiotics, i.e., Lactobacillus plantarum K90 and L. paracasei CD4, showed similar effects when administrated in diet to C. elegans [42]. Also, Bifidobacteria contribute to many beneficial effects on nematode physiology, longevity, and oxidative stress responses [12,41,43]. However, further experiments showed that the oxidative stress response was different, depending on the formulation administered to the nematodes.…”

“…Diets based on bacteria have actually been demonstrated to play an important role in the control of nematodes lifespan [11]. Several studies on probiotic-fed nematodes have investigated functional aspects of anti-aging and innate immunity, exploring multiple genetic pathways that determine longevity [12][13][14]. Probiotic bacteria have also been reported having pro-longevity and anti-aging functions on worms [14].…”

Inhibition of the neuromuscular acetylcholine receptor with atracurium activates FOXO/DAF-16-induced longevity

“…Having determined that the lifespan extension induced by atracurium is dependent on daf-16, we next aimed to validate that atracurium treatment causes physical translocation of daf-16 to the nucleus. To investigate localization of DAF-16, we employed a transgenic C. elegans strain that expresses DAF-16 tagged with GFP (Zhao et al, 2017). Heat stress activates DAF-16, so we utilized it as a positive control for DAF-16 localization to nuclei of neurons within the heads of the mutant worms (Lin et al, 2018;Figure 4A,B).…”

Curative Treatment of Candidiasis by the Live Biotherapeutic Microorganism Lactobacillus rhamnosus Lcr35® in the Invertebrate Model Caenorhabditis elegans: First Mechanistic Insights

“…To elucidate the mechanisms involved in the action of Lcr35 ® against C. albicans, we studied the expression of seven C. elegans genes (Table 2) divided into three groups: daf-2 and daf-16 (insulin signaling pathway) involved in host longevity and antipathogenicity response, sek-1 and pmk-1 (p38 MAPK signaling pathway) which concern the immunity reaction as well as abf-2, cnc-4 and fipr-22/fipr-23 which encode antimicrobial proteins. The interest in targeting these genes has been demonstrated by various studies showing that the insulin and p38 MAPK pathways were involved in the pro-longevity properties of lactobacilli and bifidobacteria [12,[18][19][20], while the antimicrobial genes were involved in the anti-Candida effect [21]. In comparison with the E. coli OP50 control condition, we noted that Lcr35 ® induced an overexpression of daf-16 (p = 0.0004) and had no effect on daf-2 (p = 0.9459), while C. albicans tended to induce an up regulation of daf-2 (p = 0.0922) and a down-regulation of daf-16 (p = 0.4959).…”