Ganoderma lucidum methyl ganoderate E extends lifespan and modulates aging-related indicators in Caenorhabditis elegans

Methyl Ganoderate E (MGE) is a triterpenoid derived from Ganoderma lucidum (Reishi), an edible mushroom, commonly processed into food forms such as soups, drinks, culinary dishes, and supplements. MGE has been shown to inhibit 3T3-L1 murine adipocyte differentiation when combined with other G. lucidum triterpenes. However, the specific effect of MGE on biological processes remains unknown. In this study, we present the first evidence of MGE's anti-aging effect in Caenorhabditis elegans. Through our screening process using the UPR^ER regulation ability, we evaluated a library of 74 pure compounds isolated from G. lucidum, and MGE exhibited the most promising results. Subsequent experiments demonstrated that MGE extended the lifespan by 26% at 10 μg ml^-1 through daf-16, hsf-1, and skn-1-dependent pathways. MGE also enhanced resistance to various molecular stressors, improved healthspan, increased fertility, and reduced the aggregation of alpha-synuclein and amyloid-beta. Transcriptome data revealed that MGE promoted processes associated with proteolysis and neural activity, while not promoting cell death processes. Collectively, our findings suggest that G. lucidum MGE could be considered as a potential anti-aging intervention, adding to the growing list of such interventions.