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J. Cachexia Sarcopenia Muscle, Feb 2025, 16 (1) e13710 | https://doi.org/10.1002/jcsm.13710
A Natural Autophagy Activator Castanea crenata Flower Alleviates Skeletal Muscle Ageing
So-HyunPark1,2, Pyeong Geun Choi1,2, Hee-Soo Kim1,2, Eunyoung Lee1, Da-Hye Lee1,3, Min Jung Kim4, Daedong Kim1,2, Hyo-Deok Seo1, Jeong-Hoon Hahm1, Tae-Il Jeon5, Yang-Hoon Huh6, Jiyun Ahn1,2, Tae-Youl Ha1,2, Chang Hwa Jung1,2
1Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea
2Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do, Republic of Korea
3Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
4Personalized Diet Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea
5Department of Animal Science, Chonnam National University, Gwangju, Republic of Korea
6Electron Microscopy Research Center, Korea Basic Science Institute, Ochang, Chungbuk, Republic of Korea
Correspondence: Chang Hwa Jung
1Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea
2Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do, Republic of Korea
3Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
4Personalized Diet Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea
5Department of Animal Science, Chonnam National University, Gwangju, Republic of Korea
6Electron Microscopy Research Center, Korea Basic Science Institute, Ochang, Chungbuk, Republic of Korea
Correspondence: Chang Hwa Jung
Abstract
Background: Sarcopenia, 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.
Methods: To 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.
Results: CCFE 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.
Conclusions: CCFE 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.
Methods: To 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.
Results: CCFE 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.
Conclusions: CCFE 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.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-03)
- 국내(교신)+국외 연구진
- 생명과학 > 식품학
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