Combined effects of a low-dose multi-target supplement (CaHMB, CBP, and HA) on delaying musculoskeletal aging.

Age-related musculoskeletal diseases underscore the importance of comprehensive dietary interventions. The individual benefits of calcium β-hydroxy-β-methylbutyrate (CaHMB), colostrum basic protein (CBP), and hyaluronic acid (HA) on the musculoskeletal system have been well documented; however, their combined effects remain unclear. This study aims to investigate the effects of combined supplementation with CaHMB, CBP, and HA on age-related musculoskeletal degeneration and to explore the underlying mechanisms, with a particular focus on the muscle-bone axis. Twelve-month-old male C57BL/6J mice received a 6-month dietary intervention. The combination (COM) group was supplemented with CaHMB, CBP, and HA at substantially reduced doses (37.5%, 20%, and 14%, respectively). The COM group showed higher lean mass (18%) and a greater muscle cross-sectional area (35%) compared to the OLD group, with significantly enhanced grip strength by 41% and exercise performances. The COM group presented less decline in whole-body bone mineral density (5%) than the OLD group. The bone microstructure was improved by increasing the bone volume fraction and trabecular thickness/number, while a decrease in trabecular separation was observed in the COM group. Musculoskeletal improvements either matched or surpassed the benefits of individual components. Mechanistically, interventions modulated the key mediators of the muscle-bone axis, significantly upregulating beneficial myokines (irisin and IGF-1) and osteokine osteocalcin, while downregulating negative regulators (myostatin and sclerostin). These changes were correlated with the observed phenotypic enhancements. The low-dose combination of CaHMB, CBP, and HA provides comprehensive benefits against age-related muscle and bone loss, likely by modulating the muscle-bone axis, and outperforms individual components. Our findings support its potential as a multi-targeted nutritional strategy for the aging population.