Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration

Abstract

Intervertebral disc degeneration (IVDD) refers to the aging and degenerative diseases of intervertebral disc components such as nucleus pulposus, annulus fibrosus, and cartilage endplate, and is the main cause of chronic low back pain. Over the past few years, many researchers around the world concerned that the degeneration of nucleus pulposus (NP) cells plays the main role in IVDD. The degeneration of NP cells is caused by a series of pathological processes, including oxidative stress, inflammatory response, apoptosis, abnormal proliferation, and autophagy. Interestingly, many studies have found a close relationship between the senescence of NP cells and the progression of NP degeneration. The classical aging pathways also have been confirmed to be involved in the pathological process of IVDD. Moreover, several anti-aging drugs have been used to treat IVDD by inhibiting NP cells senescence, such as proanthocyanidins, resveratrol and bone morphogenetic protein 2. Therefore, this article will systematically list and discuss aging, cell senescence, the pathogenesis and targeted therapies of IVDD, in order to provide new ideas for the treatment of IVDD in the future.

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems

“…9 When it comes to the structural integrity and functional maintenance of the IVD, the ECM within the NP area plays a crucial role. 10 As a result, the NP assumes a significant role in the diagnosis, management, and prevention of IVDD.…”

“…Additionally, it is worth noting that NP cells are the primary cell population to undergo apoptosis when nutrient supply to the IVD falls below the normal levels . When it comes to the structural integrity and functional maintenance of the IVD, the ECM within the NP area plays a crucial role . As a result, the NP assumes a significant role in the diagnosis, management, and prevention of IVDD.…”

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

“…Intervertebral disc degeneration (IDD) is the pathophysiological condition of the progressive structural failure of the IVD that gradually allows the vascularization and innervation of the otherwise avascular and poorly innervated tissue, ultimately leading to chronic inflammation and pain [ 6 ]. IDD pathogenesis is a complicated process, the combined result of the stressful conditions prevailing in the IVD microenvironment mentioned above (nutrient deprivation, hypoxia, oxidative stress, mechanical stress, hyperosmotic stress), transient inflammatory responses, genetic predisposition and aging.…”

“…Nevertheless, accumulation of senescent cells (e.g., due to organismal aging) may severely impair tissue microarchitecture via their SASP, substantially contributing to the manifestation or promotion of age-associated disorders [ 21 , 22 ]. After the first report on the existence of senescent cells in human IVDs by Roberts et al [ 25 ], an enhanced number of senescent cells in aged and degenerated IVDs has been identified and confirmed [ 26 ], even very early in life [ 6 ]. Given the extremely low percentage of proliferating IVD cells in healthy tissues measured in vivo, senescence of IVD cells is most plausible to be SIPS as a response to the stresses prevailing in the tissue mentioned above (i.e., nutrient, hyperosmotic, hypoxic, mechanical and oxidative stress) rather than replicative [ 27 ].…”

“…Besides its impact on the quality of life, LBP results in a serious economic load, stemming from the direct costs of the healthcare system (including medications and care provided by medical doctors and practitioners) for the prevention and treatment of LBP-caused disability, as well as from the indirect costs due to activity limitation, decrease in productivity, absenteeism and early retirement from work [ 5 ]. The etiology of LBP is multifactorial; however, intervertebral disc degeneration has been yet indisputably considered a major contributor, if not its primary cause [ 6 ].…”