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.

TRPC6 in simulated microgravity of intervertebral disc cells

“…However, variability in the basal levels of senescence (and proliferation capacity) between donors was present, as these differed with respect to age, pathology, degeneration grade and mixture of NP and AF tissue. Senescence in vivo is not only associated with the degree of disc degeneration [45], but also varies between NP and AF [20]. Furthermore, pro-inflammatory cytokines may trigger cell senescence [45], and these may not only be secreted by resident IVD cells, but also by invading immune cells found predominantly in IVD herniation samples [46].…”

“…Senescence in vivo is not only associated with the degree of disc degeneration [45], but also varies between NP and AF [20]. Furthermore, pro-inflammatory cytokines may trigger cell senescence [45], and these may not only be secreted by resident IVD cells, but also by invading immune cells found predominantly in IVD herniation samples [46]. Despite the differences in basal levels of senescence and proliferation capacity stemming from disparities in patient characteristics, we were able to show that microgravity and TRPC channel inhibition both increased cell senescence and decreased cell proliferation.…”

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

“…Intervertebral disc degeneration is a disease that is positively correlated with aging [37, 38]. With the increase in the population of elderly people around the world, disc degeneration has attracted more and more attention [39].…”

N-Cadherin Attenuates High Glucose-Induced Nucleus Pulposus Cell Senescence Through Regulation of the ROS/NF-κB Pathway

“…NP cell senescence is also a classical cellular feature in degenerative disc NP tissue, which decreases NP matrix content and ultimately attenuates disc function [6]. Previous epidemiological studies reported that DM patients exhibit a higher incidence of disc degenerative diseases than patients without DM, and DM patients with disc degenerative diseases are much younger than non-DM patients [4, 7, 8].…”