Oxidative stress-induced senescence markedly increases disc cell bioenergetics

Patil, Prashanti; Falabella, Micol; Saeed, Amal; Lee, Dayeong; Kaufman, Brett A.; Shiva, Sruti; Croix, Claudette St.; Houten, Ben Van; Niedernhofer, Laura J.; Robbins, Paul D.; Lee, Joon; Sowa, Gwendolyn; Vo, Nam

doi:10.1016/j.mad.2019.04.006

Cited by 29 publications

(32 citation statements)

References 51 publications

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“…Hartman et al showed that mitochondria undergo morphological changes with aging as the number of mitochondria reduces while mean volume per mitochondria is enhanced in NP cells [ 47 ]. In contrast, enhancement of ATP synthase activity, ATP production, and mitochondrial numbers were reported in senescent NP cells [ 60 ]. Taken together, there is an interplay between mitochondrial dysfunction, aging, and cell senescence in the onset and progression of IVD degeneration; however, it is presently unclear as to which process comes first.…”

Section: Mitochondrial Dysfunction In Ivd Degenerationmentioning

confidence: 99%

Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

2021

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The prevalence of rheumatic and musculoskeletal diseases (RMDs) including osteoarthritis (OA) and low back pain (LBP) in aging societies present significant cost burdens to health and social care systems. Intervertebral disc (IVD) degeneration, which is characterized by disc dehydration, anatomical alterations, and extensive changes in extracellular matrix (ECM) composition, is an important contributor to LBP. IVD cell homeostasis can be disrupted by mitochondrial dysfunction. Mitochondria are the main source of energy supply in IVD cells and a major contributor to the production of reactive oxygen species (ROS). Therefore, mitochondria represent a double-edged sword in IVD cells. Mitochondrial dysfunction results in oxidative stress, cell death, and premature cell senescence, which are all implicated in IVD degeneration. Considering the importance of optimal mitochondrial function for the preservation of IVD cell homeostasis, extensive studies have been done in recent years to evaluate the efficacy of small molecules targeting mitochondrial dysfunction. In this article, we review the pathogenesis of mitochondrial dysfunction, aiming to highlight the role of small molecules and a selected number of biological growth factors that regulate mitochondrial function and maintain IVD cell homeostasis. Furthermore, molecules that target mitochondria and their mechanisms of action and potential for IVD regeneration are identified. Finally, we discuss mitophagy as a key mediator of many cellular events and the small molecules regulating its function.

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Section: Mitochondrial Dysfunction In Ivd Degenerationmentioning

confidence: 99%

Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

2021

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“…45 This could be linked to the induction of cell senescence after oxidative stress which has been shown to increase mitochondrial respiration, most likely to fuel the synthesis and secretion of senescence-associated proteins. 46,47 Transcriptomic analysis of mitochondrial complex subunits from the dermis of subjects of different ages also shows an initial upregulation of the majority of genes between ages 20 and 50, followed by a downregulation thereafter. 48 The same paper show that complexes encoded by both nDNA and mtDNA are more responsive to protective intervention than the likes of complex II which is only encoded by nDNA.…”

Section: F I G U R Ementioning

confidence: 99%

Adaptive responses to air pollution in human dermal fibroblasts and their potential roles in aging

et al. 2021

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“…Senescent cells have been found to be increased with age and degeneration of human IVD [63,64]. Interestingly, senescence of IVD cells is one of the cascade events of mitochondrial dysfunction [65]. As reported, the mitochondria's role in senescent process was closely associated with overproduction of ROS that initials the related signaling networks to facilitate the senescent phenotype [66].…”

Section: Mitochondrial Dysfunction and Senescencementioning

confidence: 83%

Mitochondrial Dysfunction in Intervertebral Disc Degeneration: From Pathogenesis to Therapeutic Target

Tao

Jin

2020

Oxidative Medicine and Cellular Longevity

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Mitochondria are cytosolic organelles essential for cellular function and survival. The function of mitochondria is maintained by mitochondrial quality control systems including mitochondrial fission and fusion to adapt the altered environment and mitophagy for removal of damaged mitochondria. Mitochondrial dysfunction is closely involved in aging-related diseases. Intervertebral disc (IVD) degeneration, an aging-associated process, is the major contributor to low back pain. Growing evidence has suggested that the mitochondrial function in IVD cells is severely compromised during the degenerative process of IVD, and dysfunctional mitochondria along with impaired mitochondrial dynamics and mitophagy cause a series of cascade reactions that have been implicated in increased oxidative stress, senescence, matrix catabolism, and apoptosis of IVD cells, thereby contributing to the degeneration of IVD. Accordingly, therapies that target mitochondrial dysfunction and related mechanisms, such as ROS generation, mitophagy, and specific molecules and signaling, hold great promise. The present review summarizes the current state of the role of mitochondrial dysfunction in the pathophysiology of IVD degeneration and potential therapeutic strategies that could be developed.

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Oxidative stress-induced senescence markedly increases disc cell bioenergetics

Cited by 29 publications

References 51 publications

Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

Adaptive responses to air pollution in human dermal fibroblasts and their potential roles in aging

Mitochondrial Dysfunction in Intervertebral Disc Degeneration: From Pathogenesis to Therapeutic Target

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