Association of α-Klotho with anti-aging effects of Ganoderma lucidum in animal models

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-03-07 DOI:10.1016/j.jep.2025.119597

Xiaojing Liu , Jiamin Zhao , Jia Liu , Yan Huang , Wei Deng , Luwen Yan , Ming Cui , Xinhua Pan , Huiwen Xiao , Xingzhong Liu

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Abstract

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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民族药理学意义：衰老是一个复杂而普遍的过程，其特点是多个器官的结构和功能衰退。灵芝是一种著名的传统中药真菌，其抗衰老特性早已得到公认。然而，对其潜在机制的了解仍不全面：研究目的：本研究旨在探讨灵芝的抗衰老作用及其内在机制：我们使用自然衰老、D-半乳糖（D-gal）诱导衰老和辐射诱导早衰小鼠模型，研究了裸冠菊孢子-破损孢子粉（Gl-SBSP）对秀丽隐杆线虫（C. elegans）寿命和多器官衰老的抗衰老作用。我们评估了 elegans 的寿命、生殖能力、体长、咽部抽动、身体弯曲、脂肪和脂褐质水平以及活性氧（ROS）积累。小鼠的组织病理学染色、全血细胞计数和酶联免疫吸附试验（ELISA）被用来评估组织损伤，而定量实时 PCR（RT-qPCR）被用来检测小肠屏障的完整性。采用免疫印迹（WB）和免疫组织化学（IHC）分析α-Klotho（α-Klotho）在肾脏、血液和尿液中的分布：结果：Gl-SBSP能明显延长秀丽隐杆线虫的寿命，提高其繁殖能力和活动能力，降低脂褐质和ROS水平。在自然老化的小鼠中，Gl-SBSP 能增强其体貌和性能。此外，在所有衰老模型中，Gl-SBSP 还能缓解结肠、脾脏、肾脏、肝脏和小肠等多个器官与衰老相关的结构和功能衰退。生化分析表明，Gl-SBSP提高了肾组织中跨膜α-Klotho（mα-Klotho）和可溶性α-Klotho（sα-Klotho）的水平，并升高了血清和尿液中的α-Klotho水平：本研究首次证明了绿藻在动物模型中具有与α-Klotho相关的抗衰老作用，凸显了其作为抗衰老干预措施的潜力。

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.