3,3'-Diindolylmethane ameliorates muscle atrophy by modulating mitochondrial function and calcium homeostasis

Area of Science:

• Biochemistry
• Molecular Biology
• Gerontology

Background:

• Sarcopenia, characterized by muscle mass and function loss, has limited treatment options.
• Mitochondrial dysfunction and disrupted calcium signaling are key to muscle atrophy.
• 3,3'-Diindolylmethane (DIM) shows potential for sarcopenia due to improved bioavailability.

Purpose of the Study:

• To evaluate the therapeutic efficacy of DIM in sarcopenia across multiple models.
• To elucidate the molecular mechanisms by which DIM counteracts muscle atrophy.

Main Methods:

• Utilized three models: dexamethasone-induced murine muscle atrophy, Caenorhabditis elegans aging, and C2C12 myotube atrophy.
• Employed histopathology, immunofluorescence, fluorescent probes, western blot, and flow cytometry for evaluation.

Main Results:

• DIM improved muscle strength and quality in mice, extended C. elegans lifespan, and reduced myotube atrophy.
• DIM mitigated mitochondrial dysfunction by reducing reactive oxygen species and preserving membrane potential.
• DIM enhanced store-operated calcium entry (SOCE) via stromal interaction molecule 1, promoting differentiation and preventing atrophy.

Conclusions:

• DIM demonstrates efficacy in combating sarcopenia across murine, C. elegans, and cellular models.
• DIM enhances SOCE by improving mitochondrial function, restoring calcium homeostasis, and alleviating muscle atrophy.
• DIM represents a promising therapeutic agent for sarcopenia with novel mechanistic insights.