Active Hexose Correlated Compound Extends the Lifespan and Increases the Thermotolerance of Nematodes

Abstract

Background: Active hexose correlated compound (AHCC) is the extract from cultured mycelia of Lentinula edodes, a species of Basidiomycetes mushroom. AHCC contains various polysaccharides, including partially acylated <-1,4-glucan, which is one of its major constituents. The application of AHCC has been markedly increased in complementary and alternative medicine as a functional food because AHCC improved the prognosis of postoperative hepatocellular carcinoma patients. AHCC has anti-inflammatory and antioxidant effects, such as the suppression of nitric oxide production in hepatocytes. AHCC might affect resistance to environmental stress, which is assumed to play a pivotal role in the longevity of many organisms.Objective: To investigate the effect of AHCC on longevity, we measured the lifespan of the nematode Caenorhabditis elegans, a model animal that is widely used to assess longevity. We also examined the effect of AHCC on resistance to heat stress, i.e., thermotolerance.Methods: The lifespan of C. elegans animals grown on media in the absence or presence of AHCC at 20°C was evaluated. Thermotolerance assays were performed at 35°C, the restrictive temperature of the animals. The effects of AHCC on lifespan and thermotolerance were analyzed with longevity mutants. Expression levels of stress-related genes, including heat shock genes, were measured by strand-specific reverse transcription-polymerase chain reaction after heat shock.Results: Wild-type C. elegans animals exhibited a longer mean lifespan by up to 10% in the presence of AHCC in the growth media than animals in the absence of AHCC. Furthermore, AHCC markedly increased thermotolerance at 35°C. Epistasis analyses showed that lifespan extension by AHCC at least partly required two longevity-promoting transcription factors: DAF-16 (C. elegans homolog of FOXO) and HSF-1 (C. elegans homolog of heat shock transcription factor 1). After heat shock, AHCC activated the transcription of the heat shock genes, which are the targets of HSF-1. Similarly, the expression of hsf-1 mRNA was elevated following AHCC treatment. Recently, natural antisense transcripts were shown to regulate mRNA stability at the posttranscriptional level. In nematodes, AHCC increased the natural antisense transcript of the hsf-1 gene.Conclusion: AHCC conferred lifespan extension and thermotolerance to C. elegans. Our analyses suggest that the beneficial effects of AHCC on longevity are involved in the activation of at least two transcription factors, DAF-16 and HSF-1, most likely through an antisense transcript-mediated mechanism.Keywords: longevity, heat stress resistance, HSF, FOXO, heat shock gene