Cellular Senescence in Intervertebral Disc Aging and Degeneration
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Purpose of review
Age is a major risk factor for multiple disease pathologies, including chronic back pain, which stems from age-related degenerative changes to intervertebral disc tissue. Growing evidence suggests that the change in phenotype of disc cells to a senescent phenotype may be one of the major driving forces of age-associated disc degeneration. This review discusses the known stressors that promote development of senescence in disc tissue and the underlying molecular mechanisms disc cells adopt to enable their transition to a senescent phenotype.
Increased number of senescent cells has been observed with advancing age and degeneration in disc tissue. Additionally, in vitro studies have confirmed the catabolic nature of stress-induced senescent disc cells. Several factors have been shown to establish senescence via multiple different underlying mechanisms, including the NF-κB, Wnt/B-Catenin, and SIRT1 pathways.
Cellular senescence can serve as a therapeutic target to combat age-associated disc degeneration. However, whether the different stressors utilizing different signaling networks establish different kinds of senescent types in disc cells is currently unknown and warrants further investigation.
KeywordsAging Intervertebral disc degeneration Cellular senescence
The authors thank Jessa Darwin for her editorial assistance.
This work was made possible in part by the Public Health Service grants R01 AG044376-01 (NV), P01-AG043376 (LJN and PDR) and U19 AG056278 (LJN and PDR) from the National Institute of Health, the Glenn Foundation (LJN) and UPMC Department of Orthopaedic Surgery.
Compliance with Ethical Standards
Conflict of Interest
Prashanti Patil, Joon Lee, Gwendolyn Sowa, and Nam Vo each declare no potential conflicts of interest.
Laura J. Niedernhofer is an SAB member for Innate Biologics and Castle Creek and reports a patent pending.
Paul D. Robbins is an SAB member for Innate Biologics, Tissuegene, Unicyte, Engene, and Genascence and co-founder of Genascence. Dr. Robbins also reports a patent pending.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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