A Natural Autophagy Activator Castanea crenata Flower Alleviates Skeletal Muscle Ageing

Area of Science:

• Gerontology
• Cellular Biology
• Nutritional Science

Background:

• Sarcopenia, age-related muscle loss, impacts quality of life and mortality.
• Autophagy is vital for muscle health and maintaining muscle function with age.
• Natural autophagy activators offer potential therapeutic strategies for muscle ageing.

Purpose of the Study:

• Identify natural compounds that activate autophagy.
• Evaluate the efficacy of Castanea crenata flower extract (CCFE) in mitigating skeletal muscle ageing.
• Investigate the molecular mechanisms underlying CCFE's effects on muscle health.

Main Methods:

• Screened 493 natural products to identify CCFE as an autophagy activator.
• Assessed CCFE's impact on cellular senescence in vitro (C2C12 cells).
• Administered CCFE to aged mice (18 months) for 3 months, evaluating exercise capacity, mitochondrial function, and autophagic flux.

Main Results:

• CCFE significantly enhanced autophagic flux and reduced cellular senescence markers.
• In aged mice, CCFE improved muscle weight, exercise performance, and grip strength.
• CCFE alleviated mitochondrial dysfunction, activated AMPK, and inhibited Atg5 acetylation, restoring autophagy.

Conclusions:

• CCFE effectively counteracts skeletal muscle ageing by restoring autophagic flux and preventing mitochondrial dysfunction.
• The extract modulates AMPK and EP300 activity, with ellagic acid and polyamines contributing to its effects.
• CCFE presents a promising therapeutic strategy for sarcopenia and healthspan extension, warranting further clinical investigation.