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Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review.

ABSTRACT: Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of aging-associated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype-SASP) that plays a physiological role in embryonic development and healing processes. However, DNA damage and oxidative stress that occur during aging cause the accumulation of senescent cells, which through their SASP bring about deleterious effects on multiple organ and systemic functions. Ablation of senescent cells through genetic or pharmacological means leads to improved life span and health span in animal models, and preliminary evidence suggests it may also have a positive impact on human health. Thus, strategies to reduce or eliminate the burden of senescent cells or their products have the potential to impact multiple clinical outcomes with a single intervention. In this review, we touch upon the basics of cell senescence and summarize the current state of development of therapies against cell senescence for human use.

SUBMITTER: Amaya-Montoya M

PROVIDER: S-EPMC7140757 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review.

Amaya-Montoya Mateo M Pérez-Londoño Agustín A Guatibonza-García Valentina V Vargas-Villanueva Andrea A Mendivil Carlos O CO

Advances in therapy 20200317 4

Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of aging-associated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype-SASP) that plays a physiological role in ...[more]

PMID: 32185730

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Project description:Cellular senescence is a homeostatic biological process characterized by a permanent state of cell cycle arrest that can contribute to the decline of the regenerative potential and function of tissues. The increased presence of senescent cells in different neurodegenerative diseases suggests the contribution of senescence in the pathophysiology of these disorders. Although several factors can induce senescence, DNA damage, oxidative stress, neuroinflammation, and altered proteostasis have been shown to play a role in its onset. Oxidative stress contributes to accelerated aging and cognitive dysfunction stages affecting neurogenesis, neuronal differentiation, connectivity, and survival. During later life stages, it is implicated in the progression of cognitive decline, synapse loss, and neuronal degeneration. Also, neuroinflammation exacerbates oxidative stress, synaptic dysfunction, and neuronal death through the harmful effects of pro-inflammatory cytokines on cell proliferation and maturation. Both oxidative stress and neuroinflammation can induce DNA damage and alterations in DNA repair that, in turn, can exacerbate them. Another important feature associated with senescence is altered proteostasis. Because of the disruption in the function and balance of the proteome, senescence can modify the proper synthesis, folding, quality control, and degradation rate of proteins producing, in some diseases, misfolded proteins or aggregation of abnormal proteins. There is an extensive body of literature that associates cellular senescence with several neurodegenerative disorders including Alzheimer's disease (AD), Down syndrome (DS), and Parkinson's disease (PD). This review summarizes the evidence of the shared neuropathological events in these neurodegenerative diseases and the implication of cellular senescence in their onset or aggravation. Understanding the role that cellular senescence plays in them could help to develop new therapeutic strategies.

Dataset Information

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review.

Publications

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review.

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