Objective: To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging. Methods: Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks. Forelimb grip strength, hanging performance, and locomotor activity were assessed. Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis, contractile-marker features, senescence- and DNA damage-associated markers, inflammatory signaling, and mitochondrial proteins. Oxidative status was assessed by determining antioxidant capacity, lipid peroxidation, and oxidative DNA damage. Transcriptomic profiling was also performed, and selected targets were validated by quantitative RT-PCR and immunostaining. In addition, differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract; senescence-associated β-galactosidase, DNA damage signaling, and cell viability were measured. Results: Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion. It also reduced collagen deposition, preserved contractile-marker immunoreactivity, attenuated senescence- and inflammation-associated signals, and increased mitochondrial protein immunoreactivity. Oxidative DNA damage was notably reduced by nacre extract. Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression, which were supported by tissue-level validation. In C2C12 myotubes, nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability. Conclusions: Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress, inflammation, mitochondrial features, and cellular senescence.
Kimoto et al. (Wed,) studied this question.