DNA double-strand break (DSB) increased in the progress of sarcopenia caused by 1,25(OH)₂D₃ deficiency, which contributed to the phosphorylation of ataxia telangiectasia-mutated genes (ATM) and ataxia telangiectasia and Rad-3-related protein (ATR), and then caused DNA damage response (DDR). GATA4 was upregulated as a result of DDR, bound to the promoter region, and increased the transcriptional level of Rela. Bmi-1 overexpression ameliorated sarcopenia in 1,25(OH)₂D₃-deficient mice by promoting the ubiquitination and degradation of GATA4 by binding to RING1B and subsequently decreased Rela transcription, which inhibited NF-κB-p65 signaling-mediated SASP.