Therapeutic silicate biomaterials for sarcopenia treatment by inhibiting inflammation and enhancing muscle regeneration through regulation of Sarcolipin/SIRT signaling pathway

Based on the observation of silicon content decrease in the muscles and serum with aging, this study proposes a silicate bioactive material based therapy for treating sarcopenia. Two therapeutic strategies were designed. One utilizes calcium silicate (CS) hydrogel for localized intramuscular treatment, and the other employs CS solution for systemic treatment through Intravenous injection. Both treatments restore silicon levels in the muscles and serum of aging mice, and show therapeutic effects on sarcopenia. Specifically, the CS hydrogel demonstrates more pronounced short-term efficacy in promoting local muscle regeneration, while the CS solution exhibits superior outcomes in modulating the overall condition of aging mice. The fundamental mechanism of the CS treatments on sarcopenia may involve the direct regulation of the SIRTs signaling pathway by silicate ions released from CS, as well as the indirect regulation of SIRTs pathway via the suppression of Sarcolipin (SLN) overexpression by silicate ions. Specifically, silicate ions directly upregulate SIRT1 expression in macrophages and on one side promote NF-kB deacetylation to inhibit M1 polarization, and on the other side facilitate STAT3 deacetylation to inhibit M2 polarization, ultimately reducing the expression of inflammatory factors (TNF-α, IL-6) and fibrotic factors (IL-10, TGF-β). Meanwhile, silicate ions directly upregulate SIRT3 in myoblasts, leading to the promotion of STAT3 dephosphorylation, inhibits mitochondrial reactive oxygen species (ROS) secretion, and enhances the expression of MyoD, MyoG, and Myosin, and accelerates myogenic differentiation. This bioactive CS based therapy provides a new approach for combating sarcopenia.