Bazi Bushen attenuates musculoskeletal degeneration in Ercc1^+/- mice

Age-related musculoskeletal degeneration, characterized by the coexistence of sarcopenia and osteoporosis, represents a growing health burden among older adults. Current therapeutic strategies generally target either skeletal muscle or bone, and few are designed to address both tissues.

Female wild-type (WT) and Ercc1^+/- mice were assigned to four groups (n = 6 per group): WT controls, untreated Ercc1^+/- mice, and Ercc1^+/- mice treated with nicotinamide mononucleotide (NMN; 300 mg/kg/day) or Bazi Bushen (BZBS; 2 g/kg/day). Body composition, skeletal muscle mass, and grip strength were assessed, while bone microarchitecture and femoral mechanical properties were evaluated using micro-computed tomography (micro-CT) and three-point bending tests, respectively. Histomorphological changes in skeletal muscle and femur were assessed using hematoxylin and eosin (H&E), Masson's trichrome, and Goldner's trichrome staining. The expression levels of the senescence-associated proteins p16 and p21 and the atrophy-related proteins Atrogin-1 and MuRF-1 were determined by Western blotting. Indirect calorimetry was used to assess whole-body energy metabolism. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), and myostatin were measured by ELISA.

Ercc1^+/- mice exhibited reduced lean mass and grip strength, skeletal muscle fiber atrophy with increased collagen deposition, impaired bone microarchitecture, and impaired femoral mechanical properties. BZBS treatment significantly ameliorated these abnormalities in skeletal muscle and bone and reduced the expression of p16, p21, Atrogin-1, and MuRF-1 in skeletal muscle. In addition, BZBS increased whole-body energy metabolism and spontaneous locomotor activity, lowered serum levels of myostatin and FSH, and increased serum estradiol levels.

BZBS improved skeletal muscle mass and function, trabecular bone microarchitecture, and bone mechanical properties in female Ercc1^+/- mice and reduced the skeletal muscle expression of proteins associated with atrophy and senescence. These improvements may be associated with increased whole-body energy metabolism and spontaneous locomotor activity, as well as lower circulating levels of myostatin and FSH and higher levels of E2. These findings provide preclinical support for further investigation of BZBS as a potential multisystem intervention for age-related musculoskeletal degeneration.