In this study, we observed reduced AMPK phosphorylation and SIRT‐1 expression in P. acnes‐infected NPCs, and pharmacological activation of AMPK and SIRT‐1 significantly reversed the reduction in mitochondrial biogenesis‐related factors, improved oxidative metabolism, and ultimately reversed P. acnes‐induced disc degeneration. The gene discussed is SIRT1; the disease is intervertebral disk degenerative disorder.