Accelerated aging of intervertebral discs in a mouse model of progeria

Vo, Nam; Seo, Hyoung‐Yeon; Robinson, Andria Rasile; Sowa, Gwendolyn; Bentley, Douglas; Taylor, Lawrence W.; Studer, Rebecca K.; Ūsas, Arvydas; Huard, Johnny; Alber, Sean; Watkins, Simon C.; Lee, Joon; Coehlo, Paulo; Wang, Dong; Loppini, Mattia; Robbins, Paul D.; Niedernhofer, Laura J.; Kang, James D.

doi:10.1002/jor.21153

Cited by 83 publications

(114 citation statements)

References 46 publications

(49 reference statements)

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“…The syndrome is characterized by accelerated aging of virtually all organ systems, all driven by failure to repair stochastic endogenous DNA damage. A murine model of XFE progeroid syndrome, Ercc1 -/Δ mice, have about 10% of the normal amount of ERCC1 protein and spontaneously develop progressive, degenerative changes that correlate strongly with natural aging (43)(44)(45)(46)(47). Thus, Ercc1 -/-mice, which have a complete absence of ERCC1 protein, and Ercc1 -/Δ mice offer a unique opportunity to investigate the mechanism by which one type of cellular damage promotes aging and whether NF-κB plays a pivotal role.…”

Section: Introductionmentioning

confidence: 99%

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

et al. 2012

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The accumulation of cellular damage, including DNA damage, is thought to contribute to aging-related degenerative changes, but how damage drives aging is unknown. XFE progeroid syndrome is a disease of accelerated aging caused by a defect in DNA repair. NF-κB, a transcription factor activated by cellular damage and stress, has increased activity with aging and aging-related chronic diseases. To determine whether NF-κB drives aging in response to the accumulation of spontaneous, endogenous DNA damage, we measured the activation of NF-κB in WT and progeroid model mice. As both WT and progeroid mice aged, NF-κB was activated stochastically in a variety of cell types. Genetic depletion of one allele of the p65 subunit of NF-κB or treatment with a pharmacological inhibitor of the NF-κB-activating kinase, IKK, delayed the age-related symptoms and pathologies of progeroid mice. Additionally, inhibition of NF-κB reduced oxidative DNA damage and stress and delayed cellular senescence. These results indicate that the mechanism by which DNA damage drives aging is due in part to NF-κB activation. IKK/NF-κB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging.

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Section: Introductionmentioning

confidence: 99%

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

et al. 2012

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“…IDD pathogenesis is affected by various factors including genes, life styles, biophysics, and other chronic diseases, making it one complicated and refractory disease that severely affect patient's health and life quality [11]. In clinics, major approaches for treating IDD include surgery, conservative treatment, cell therapy or gene therapy, all of which may not achieve satisfactory results [12].…”

Section: Discussionmentioning

confidence: 99%

Effects of plasma vaporization ablation on expression of inflammatory factors in rabbit model of intervertebral disc degeneration

Peng¹,

Xu²,

Shan³

et al. 2018

biomedicalresearch

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Intervertebral Disc Degeneration (IDD) is one common disease presented as wrist pain. Plasma vaporization ablation is a novel method treating IDD. This study utilized vaporization ablation on rabbit IDD model, whose expression of inflammatory factors was analysed along with the correlation with plasma vaporization ablation. Rabbit IDD model was generated by puncture approach and treated with plasma vaporization ablation. Control group received no treatment after surgery. MRI scanning was performed on rabbit intervertebral disc. Serum and intervertebral disc tissue samples were collected and tested for expression of Tumor Necrosis Factor α (TNF-α), Interleukin-2 (IL-2) and IL-4 by Enzyme Linked Immunosorbent Assay (ELISA) or Immunohistochemistry (IHC) methods. 2 w after puncture, rabbit had rupture of intervertebral disc fibrous ring, plus change of low-strength T2 signal but not in T1 signal. 4 w after surgery, model rats had further decreased intervertebral disc T2 signals. Both serum and intervertebral disc levels of TNF-α, IL-2 and IL-4 were significantly elevated in model group, and were gradually decreased with elongated treatment (p<0.05). Plasma vaporization ablation can decrease expression of TNF-α, IL-2 and IL-4 in both serum and intervertebral disc tissues, probably forming one mechanism of IDD.

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“…6,7 The development of IDD is related to genetic predisposition, excessive load, smoking, and the natural aging process. 8,9 Many studies on the cellular mechanisms of IDD have demonstrated the importance of maintaining extracellular matrix homeostasis, striving for a balance between the synthesis and the catabolism of its components. 10,11 However, natural history, as well as the biological mechanisms that lead to IDD, still have gaps to be filled.…”

Section: Introductionmentioning

confidence: 99%

Expression of matrix factors in the process of neovascularization of intervertebral disc

et al. 2015

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Objective: To investigate the effects of proteins products of endothelial cells (ECs) on the annulus fibrosus (AF) cell metabolism in an in vitro culture. Methods: Human AF cells were expanded in monolayer cultures and treated with proteins from the medium of cell line HMEC-1 (Human Microvascular Endothelial Cells) (125μg/ml). After 72h of treatment RNA was isolated from AF cells for analysis of gene expression and the culture medium was collected for protein expression analysis. de células af: mmp-1 243,10 veces (p < 0,05), mmp-2 1,37 veces (p < 0,05), mmp-3 39,83 veces (p < 0,05) y mmp-13 5,70 veces (p < 0,05 RESUMEN objetivo: analizar el efecto de los productos de proteína de las células endoteliales (Ces) en el metabolismo celular del anillo fibroso (af) en sistema in vitro de cultivo controlado. métodos: Las células del af humano se ampliaron en monocapa y se las trató con las proteínas obtenidas a partir de los medios de cultivo de la línea de células HmeC-1 (Human microvascular endothelial Cells) (125μg/ml). después de 72h de tratamiento, se aisló el arN de las células de af para el análisis de la expresión génica y se recogió el medio de cultivo para el análisis de expresión de la proteína. resultados: el análisis de qrt-pCr demostró una mayor expresión génica de las metaloproteinasas de matriz (mmp) en las células tratadas con productos de proteína de af en las células endoteliales, en comparación con el grupo de control

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Accelerated aging of intervertebral discs in a mouse model of progeria

Cited by 83 publications

References 46 publications

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

Effects of plasma vaporization ablation on expression of inflammatory factors in rabbit model of intervertebral disc degeneration

Expression of matrix factors in the process of neovascularization of intervertebral disc

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