Abstract
Intervertebral disc degeneration (IVDD) is the main cause of cervical and lumbar spondylosis. Over the past few years, the relevance between cellular senescence and IVDD has been widely studied, and the senescence-associated secretory phenotype (SASP) produced by senescent cells is found to remodel extracellular matrix (ECM) metabolism and destruct homeostasis. Elimination of senescent cells by senolytics and suppression of SASP production by senomorphics/senostatics are effective strategies to alleviate degenerative diseases including IVDD. Here, we review the involvement of senescence in the process of IVDD; we also discuss the potential of senolytics on eliminating senescent disc cells and alleviating IVDD; finally, we provide a table listing senolytic drugs and small molecules, aiming to propose potential drugs for IVDD therapy in the future.
Highlights
Intervertebral disc degeneration (IVDD) refers to an age-related change that mainly occurs in the lumbar intervertebral disc and often precedes other age-related changes (Adams and Roughley, 2006; Vergroesen et al, 2015)
Since the accumulation of senescent cells is the main cause of agerelated degenerative diseases, it is widely believed that removing senescent cells and reducing the production of senescence-associated secretory phenotype (SASP) can alleviate the aging-related dysfunction and improve agerelated diseases or related phenotypes (Baker et al, 2011; Zhu et al, 2015)
In the study by Novais et al (2019), the secretion of SASP was reduced and extracellular matrix (ECM) homeostasis was improved in p16INK4a KO mice, there was no significant difference in the reduction of senescent cells in the intervertebral disc and the improvement of IVDD process compared with the control group
Summary
Intervertebral disc degeneration (IVDD) refers to an age-related change that mainly occurs in the lumbar intervertebral disc and often precedes other age-related changes (Adams and Roughley, 2006; Vergroesen et al, 2015). During the process of IVDD, annulus fibrosis (AF), one of the important compositions of intervertebral disc, loses its original layer and toughness, and reticulated degeneration and hyalinization appear, while the percentage of water decreases in another component called nucleus pulposus (NP). The intervertebral disc loses its normal elasticity and tension (Roberts et al, 2006). Severe trauma or repeated inconspicuous damage may cause the annulus fibrosis to become weak or even rupture. There are two results depending on the severity of damage to AF. IVDD is considered to be one of the main causes of low back pain and lumbar herniated disc (Brinjikji et al, 2015). There are two main treatment strategies for IVDD: surgery and drug therapy
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