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Targeting senescent cells: approaches, opportunities, challenges

Cellular senescence is a hallmark of aging, whose onset is linked to a series of both cell and non-cell autonomous processes, leading to several consequences for the organism. To date, several senescence routes have been identified, which play a fundamental role in development, tumor suppression and...

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Detalles Bibliográficos
Autor principal: von Kobbe, Cayetano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949083/
https://www.ncbi.nlm.nih.gov/pubmed/31789602
http://dx.doi.org/10.18632/aging.102557
Descripción
Sumario:Cellular senescence is a hallmark of aging, whose onset is linked to a series of both cell and non-cell autonomous processes, leading to several consequences for the organism. To date, several senescence routes have been identified, which play a fundamental role in development, tumor suppression and aging, among other processes. The positive and/or negative effects of senescent cells are directly related to the time that they remain in the organism. Short-term (acute) senescent cells are associated with positive effects; once they have executed their actions, immune cells are recruited to remove them. In contrast, long-term (chronic) senescent cells are associated with disease; they secrete pro-inflammatory and pro-tumorigenic factors in a state known as senescence-associated secretory phenotype (SASP). In recent years, cellular senescence has become the center of attention for the treatment of aging-related diseases. Current therapies are focused on elimination of senescent cell functions in three main ways: i) use of senolytics; ii) inhibition of SASP; and iii) improvement of immune system functions against senescent cells (immunosurveillance). In addition, some anti-cancer therapies are based on the induction of senescence in tumor cells. However, these senescent-like cancer cells must be subsequently cleared to avoid a chronic pro-tumorigenic state. Here is a summary of different scenarios, depending on the therapy used, with a discussion of the pros and cons of each scenario.