Sirtuins in intervertebral disc degeneration: current understanding

Area of Science:

• Biomedical Science
• Molecular Biology
• Gerontology

Background:

• Intervertebral disc degeneration (IVDD) is a primary cause of lower back pain, increasing with age.
• IVDD contributes to spinal conditions like disc herniation, stenosis, and scoliosis.
• Sirtuins (SIRTs) and their activators are emerging as potential therapeutic targets for IVDD.

Purpose of the Study:

• To systematically review the role of SIRTs and their activators in intervertebral disc degeneration (IVDD).
• To elucidate the molecular mechanisms underlying SIRT-mediated regulation of IVDD.
• To discuss the impact of SIRTs on cellular processes relevant to IVDD, including senescence, inflammation, oxidative stress, and mitochondrial function.

Main Methods:

• Systematic literature search of PubMed and Web of Science databases.
• Inclusion of studies published between 2011 and 2024.
• Keywords used: "SIRT", "Sirtuin", "IVDD", "IDD", "IVD", "NP", "Intervertebral disc degeneration", "Intervertebral disc", and "Nucleus pulposus".

Main Results:

• SIRTs and numerous activators demonstrate protective effects against IVDD.
• SIRTs modulate key processes including autophagy, apoptosis, oxidative stress, and extracellular matrix degradation.
• Clinical studies confirm the benefits of SIRT activators like resveratrol and melatonin in mitigating IVDD.

Conclusions:

• SIRTs and their activators exhibit diverse mechanisms beneficial for combating IVDD.
• Understanding these roles enhances the potential for developing novel IVDD therapies.
• This review highlights challenges in translating basic SIRT research into clinical applications for IVDD treatment.