ArticleJournal of cachexia, sarcopenia and muscle2025
A Natural Autophagy Activator Castanea crenata Flower Alleviates Skeletal Muscle Ageing.
Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Huangqi Guizhi Wuwu Decoction Ameliorates Cachexia in Lung Cancer Mice Through Regulating Amino Acid Metabolism: Insights From Transcriptomics, Metabolomics and Experimental Validation.Journal of cellular and molecular medicine · 2026Article
- Review
- Mechanisms of Impaired Skeletal Muscle Regeneration and Therapeutic Approaches in Aging and Chronic Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Intrinsic Capacity, Polygenic Risk Score, and Risk of Glaucoma.Translational vision science & technology · 2026Article
- Article
- Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics.Molecular cancer · 2025Review
- Non-hormone replacement therapy to overcome premature ovarian insufficiency: advances in natural products and stem cells targeting autophagy.Frontiers in endocrinology · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
backgroundSarcopenia, characterized by a gradual decline in skeletal muscle mass and function with age, significantly impacts both quality of life and mortality. Autophagy plays a crucial role in maintaining muscle health. There is growing interest in leveraging autophagy to mitigate muscle ageing effects. The impact of natural autophagy activators on skeletal muscle ageing remains elusive. This study aims to identify natural autophagy activators and assess their effects on skeletal muscle ageing.
methodsTo discover novel autophagy activators, we screened 493 natural products and identified Castanea crenata flower extract (CCFE) as a promising candidate. We investigated the effect of CCFE on cellular senescence in C2C12 cells induced by etoposide. In animal experiments, aged mice (18 months old) were fed a diet supplemented with 0.1% and 0.2% CCFE for 3 months. We assessed exercise capacity, mitochondrial function and autophagic flux to determine the impact of CCFE on skeletal muscle ageing. The components present in CCFE were analysed using LC-MS/MS, and their functional properties were examined.
resultsCCFE enhanced autophagic flux (LC3II 80% increase, p < 0.05) and reduced senescence-associated β-galactosidase activity (32.78% decrease, p < 0.001). In aged mice, a 3-month supplementation with CCFE improved muscle weight (18% increase, p < 0.05) and function (treadmill performance increased by 60%, p < 0.5; grip strength increased by 25%, p < 0.05). It alleviated mitochondrial dysfunction (basal oxygen consumption rate increased by 59%, p < 0.05) and restored autophagy. CCFE enhanced autophagy by activating AMPK (80% increase, p < 0.01) and inhibiting Atg5 protein acetylation (65% decrease, p < 0.001), with contributions from ellagic acid and polyamines. CCFE supplementation restored polyamine levels (serum spermidine increased from 0.98 ± 0.08 to 2.22 ± 0.05 μg/mL, p < 0.001) and increased urolithin levels (serum urolithin A increased from 0 to 18.79 ± 0.062 ng/mL, p < 0.001), metabolites produced by the gut microbiome from ellagic acid in aged mice.
conclusionsCCFE effectively suppressed skeletal muscle ageing by preventing mitochondrial dysfunction and restoring autophagic flux in aged mice. It achieved this by modulating AMPK and EP300 acetyltransferase activity, with contributions from its constituents, ellagic acid and polyamines. These findings highlight the potential of CCFE as a therapeutic agent for extending healthspan and mitigating sarcopenia, providing a basis for future clinical trials.
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