Source: europepmc · Origin: KR · Wang X, Kim CY, Je JG, Roh YJ, Yang F, Yang HW, Jeon YJ. · Food & function · 2026-05-26
URL: https://pubmed.ncbi.nlm.nih.gov/42186764/
AI rationale (4/5, tier: preliminary): SirT1/PGC-1α axis activation in aging muscle model; mechanism-driven but zebrafish in vivo limits translational weight.
Diphlorethohydroxycarmalol (DPHC), a brown alga tannin isolated from <i>Ishige okamurae</i>, has been reported to stimulate skeletal muscle contraction by promoting the release of calcium ions (Ca<sup>2+</sup>) from the sarcoplasmic reticulum. Although aging is a major cause of skeletal muscle dysfunction, the effect of DPHC on age-related muscle dysfunction remains unclear. This study aims to investigate how DPHC can mitigate skeletal muscle dysfunction induced by D-galactose (D-gal)-mediated aging, utilizing both <i>in vitro</i> and <i>in vivo</i> models, and to elucidate its potential pathways. A skeletal muscle aging model was established by exposing adult zebrafish to D-gal at a concentration of 1% for 6 weeks. This model significantly reduced the zebrafish behavior and muscle mass. <i>In vitro</i>, DPHC treatment significantly increased cell viability in D-gal (200 mM)-induced C2C12 myoblasts, while significantly reducing the activity of the senescence marker senescence-associated β-galactosidase (SA-β-gal). In addition, DPHC also elevated intracellular Ca<sup>2+</sup> levels, inhibited ROS accumulation, and restored ATP production in D-gal-stimulated C2C12 myoblasts. <i>In vivo</i>, DPHC administration improved the swimming ability and skeletal muscle integrity of zebrafish. It also reduced glycogen accumulation and increased ATP levels in muscle tissue. Mechanistically, DPHC activated calcium/calmodulin-dependent protein kinase kinase 2 (CaMKKβ) in skeletal muscle and promoted AMP-activated protein kinase (AMPK) phosphorylation, thereby upregulating the expression of SirT1 and PGC-1α proteins. Overall, these findings suggest that DPHC attenuates D-gal-induced skeletal muscle dysfunction by enhancing intracellular Ca<sup>2+</sup> levels to activate the CaMKKβ-AMPK pathway to trigger the SirT1/PGC-1α axis, highlighting its potential as a therapeutic agent against age-related muscle dysfunction.