Here, we find that the senescence of macrophages leads to a decrease in the expression of Sirtuin3 (Sirt3), which in turn leads to increased basal and lipopolysaccharides (LPS)-induced protein expression of NLRP3 and facilitates the assembly of NLRP3 inflammasome in macrophages that mediates aging-related osteoporosis. Here, SIRT3 is linked to osteoporosis.