Senescence induced by irradiation revealed by immunofluorescence. Image credit: Zhang et al. (CC BY 4.0)
Back pain is among the most common health problems and is frequently caused by damage to the discs between the vertebrae, known as intervertebral discs. These discs act as cushions, allowing for movement and absorbing mechanical forces.
As people age, these discs become stiff and wear out, which is a major risk factor for back pain. Cellular senescence, a process in which cells stop dividing and start releasing harmful cell products, contributes to this degeneration by damaging the surrounding cells. In aged or degenerated intervertebral discs, the number of senescent cells is significantly increased.
The protein PDGF is a growth factor involved in cell growth and division and is widely used in the clinical setting for tissue regeneration and repair. So far, it was unknown if PDGF could slow down cellular senescence in intervertebral discs.
To find out more, Zhang et al. collected two types of cells found in intervertebral discs – the nucleus pulposus cells and the annulus fibrosus cells – from tissue samples of healthy individuals and patients with disc hernias. They then treated these cells with PDGF and analyzed their gene activity. The experiments showed that PDGF slowed cellular senescence in both cell types. In both tissues, PDGF increased the expression of genes that promote the cell cycle and decreased the expression of genes related to senescence, including those involved in oxidative stress responses and mitochondrial dysfunction. Zhang et al. also noted some tissue-specific responses to PDGF treatment, with nucleus pulposus cells responding more by reducing the activity of genes involved in metabolic pathways, and annulus fibrosus cells by deactivating genes involved in responses to mechanical stimulation experienced during daily activities.
Zhang et al. further developed a ‘cellular senescence model’ by exposing healthy cells extracted from the nucleus pulposus and the annulus fibrosus to a single dose of senescence-inducing radiation in both cell types. Immediate treatment with PDGF reduced the expression of senescence-related genes.
In summary, the study indicates that PDGF can inhibit cell senescence in intervertebral discs. The next step will be to validate these findings in animal models and clinical trials to ensure safety and effectiveness. In the future, this could lead to new strategies for developing minimally invasive therapies to inhibit or halt the progression of degenerative disc disease within the ageing spine.
