Many studies have demonstrated that Sirtuin 1, an NAD⁺-dependent deacetylase, reduces apoptosis in several different cells. However, the role of Sirtuin 1 in apoptosis of disc nucleus pulposus (NP) cells remains unclear. The present study was performed to determine whether degenerative human NP would express Sirtuin 1, and to investigate the role of Sirtuin 1 in NP cells apoptosis. Here we show that Sirtuin 1 mRNA and protein levels in disc NP from patients (< 25 years) with lumbar vertebra fracture (LVF) are greater than those in degenerative disc NP from patients (> 55 years) with lumbar disc herniation (LDH). The rate of apoptosis was far fewer in resveratrol-treated NP cells than that in siRNA transfected or nicotinamide-treated NP cells. We also tried to explore the signaling molecules that mediate the protective property of Sirtuin 1 by Western blot and inhibitor analysis. After Sirtuin 1 siRNA transfected, NP cells decreased phosphorylation of Akt, while resveratrol phosphorylated Akt. Treatment with LY294002 or Akt siRNA increased the rate of apoptosis. Our results indicate that Sirtuin 1 plays a critical role in survival of degenerative human NP cells through the Akt anti-apoptotic signaling pathway.