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Cellular Senescence in Disc Degeneration


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Posted 01 June 2023 - 10:22 AM


The better understanding developed in recent years of the harmful effects of lingering senescent cells in the tissues of older individuals has led to a burst of research into cellular senescence in many areas of medicine. One of the more active parts of the field of late, judging by number of publications, is degenerative disc disease. Therapies that can efficiently remove senescent cells may well turn out to greatly slow the widespread age-related dysfunction observed in intevertebral disc tissue.

Closely associated with aging and age-related disorders, cellular senescence is the inability of cells to proliferate due to accumulated unrepaired cellular damage and irreversible cell cycle arrest. Senescent cells are characterized by their senescence-associated secretory phenotype that overproduces inflammatory and catabolic factors that hamper normal tissue homeostasis. Chronic accumulation of senescent cells is thought to be associated with intervertebral disc degeneration (IDD) in an aging population. IDD is one of the largest age-dependent chronic disorders, often associated with neurological dysfunctions such as, low back pain, radiculopathy, and myelopathy.

Senescent cells increase in number in the aged, degenerated discs, and have a causative role in driving age-related IDD. This review summarizes current evidence supporting the role of cellular senescence on onset and progression of age-related IDD. The discussion includes molecular pathways involved in cellular senescence such as p53-p21CIP1, p16INK4a, NF-κB, and MAPK, and the potential therapeutic value of targeting these pathways. We propose several mechanisms of cellular senescence in IDD including mechanical stress, oxidative stress, genotoxic stress, nutritional deprivation, and inflammatory stress. There are still large knowledge gaps in disc cellular senescence research, an understanding of which will provide opportunities to develop therapeutic interventions to treat age-related IDD.

Link: https://doi.org/10.3390/biom13040686


View the full article at FightAging




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