Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy

Spinal disease: Exercise-induced protein protects against disc degeneration Physical exercise in rodents helps to promote expression of a protein that guards against intervertebral disc degeneration (IVDD), a major cause of lower back pain. A team from Wenzhou Medical University in China, led by Xiaolei Zhang and Aimin Wu, showed that mice and rats that participated in regular swimming sessions were less prone to IVDD, an effect mediated by a protein called irisin. Increased levels of this protein (and its precursor form, known as FNDC5) in the cells of the jelly-like tissue found in the core of spinal discs helped to enhance cellular recycling processes. This in turn prevented cell death and deterioration in the spine. Boosting the activity of FNDC5/irisin, either through drugs or exercise, could therefore help alleviate back pain and delay the progression of IVDD in humans. Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), and excessive senescence and apoptosis of nucleus pulposus (NP) cells are major pathological changes in IVDD. Physical exercise could effectively delay the process of intervertebral disc degeneration; however, its mechanism is still largely unknown. Irisin is an exercise-induced myokine released upon cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), and its levels increase after physical exercise. Here, we show that after physical exercise, FNDC5/irisin levels increase in the circulation and NP, senescence and apoptosis are reduced, autophagy is activated in NP tissue, and the progression of IVDD is delayed. Conversely, after knocking out FNDC5, the benefits of physical exercise are compromised. Moreover, the overexpression of FNDC5 in NP tissue effectively alleviated the degeneration of the intervertebral disc (IVD) in rats. By showing that FNDC5/irisin is an important mediator of the beneficial effects of physical exercise in the IVDD model, the study proposes FNDC5/irisin as a novel agent capable of activating autophagy and protecting NP from senescence and apoptosis.

Automated summary

A study has found that physical exercise promotes the expression of a protein called irisin, which protects against intervertebral disc degeneration. This discovery suggests that increasing the activity of irisin through either exercise or drugs could help alleviate back pain and slow down the progression of the disease.