title: Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration.
abstract: Intervertebral disc (IVD) degeneration is a complicated process that involves both age-related change and tissue damage caused by multiple stresses. In a degenerative IVD, cellular senescence accumulates and is associated with reduced proliferation, compromised self-repair, increased inflammatory response, and enhanced catabolic metabolism. In this review, we decipher the senescence mechanism of IVD degeneration (IVDD) by interpreting how aging coordinates with age-related, microenvironment-derived stresses in promoting disc cell senescence and accelerating IVDD. After chronic and prolonged replication, cell senescence may occur as a natural part of the disc aging process, but can potentially be accelerated by growth factor deficiency, oxidative accumulation, and inflammatory irritation. While acute disc injury, excessive mechanical overloading, diabetes, and chronic tobacco smoking contribute to the amplification of senescence-inducing stresses, the avascular nature of IVD impairs the immune-clearance of the senescent disc cells, which accumulate in cell clusters, demonstrate inflammatory and catabolic phenotypes, deteriorate disc microenvironment, and accelerate IVDD. Anti-senescence strategies, including telomerase transduction, supply of growth factors, and blocking cell cycle inhibitors, have been shown to be feasible in rescuing disc cells from early senescence, but their efficiency for disc regeneration requires more in vivo validations. Guidelines dedicated to avoiding or alleviating senescence-inducing stresses might decelerate cellular senescence and benefit patients with IVD degenerative diseases.
authors.affiliation: Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China; Surgery Research Center, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China. Electronic address: wangfengspinespine@163.com.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China; Surgery Research Center, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China. Electronic address: fzzs_1987@163.com.
authors.forename: F
authors.initials: F
authors.lastname: Cai
authors.affiliation: Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China; Surgery Research Center, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China. Electronic address: 277834792@qq.com.
authors.forename: R
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China; Surgery Research Center, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China. Electronic address: nk_james@sina.com.
authors.forename: X-H
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China; Surgery Research Center, School of Medicine, Southeast University, 87# Dingjiaqiao Road, 210009 Nanjing, China. Electronic address: wuxiaotaospine@163.com.
authors.forename: X-T
authors.initials: XT
authors.lastname: Wu
mesh_terms: D000375:Aging / Q000473:pathology*; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D013314:Stress, Mechanical
keywords: Aging; Cellular senescence; Intervertebral disc; Microenvironment