Ethnopharmacological Relevance: Aging is a complex, universal process characterized by structural and functional decline across multiple organs. Ganoderma lucidum (G. lucidum), a renowned traditional Chinese medicinal fungus, has long been recognized for its anti-aging properties. However, the underlying mechanisms remain incompletely understood.
Aim Of The Study: This study aimed to investigate the anti-aging effects of G. lucidum and its underlying mechanisms.
Materials And Methods: We investigated the anti-aging effects of G. lucidum sporoderm-broken spore powder (Gl-SBSP) on Caenorhabditis elegans (C. elegans) lifespan and aging across multiple organs using natural aging, D-galactose (D-gal)-induced aging, and radiation-induced premature senescence mouse models. In C. elegans, we assessed lifespan, reproductive capacity, body length, pharyngeal pumping, body bends, fat and lipofuscin levels, as well as reactive oxygen species (ROS) accumulation. In mice, histopathological staining, complete blood counts, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate tissue damage, while quantitative real-time PCR (RT-qPCR) was employed to access small intestine barrier integrity. Western blot (WB) and immunohistochemistry (IHC) were utilized to analyze the distribution of alpha Klotho (α-Klotho) in the kidney, blood, and urine.
Results: Gl-SBSP significantly extended C. elegans lifespan, improved reproductive capacity and mobility, and reduced lipofuscin and ROS levels. In naturally aged mice, Gl-SBSP enhanced physical appearance and performance. Additionally, Gl-SBSP alleviated aging-related structural and functional decline in multiple organs, including the colon, spleen, kidneys, liver, and small intestine, across all aging models. Biochemical analyses revealed that Gl-SBSP increased transmembrane α-Klotho (mα-Klotho) and soluble α-Klotho (sα-Klotho) levels in kidney tissue and elevated sα-Klotho levels in serum and urine.
Conclusion: This study is the first to demonstrate that G. lucidum exerts α-Klotho-associated anti-aging effects in animal models, highlighting its potential as an anti-aging intervention.
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