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SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Targeting senescent cells: approaches, opportunities, challenges
1Centro de Biología Molecular "Severo Ochoa" (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid, Madrid 28049, Spain.
Abstract:
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.
Insights
Cellular senescence, a key aging process, involves cells that can be beneficial short-term but harmful long-term. Therapies aim to clear senescent cells or inhibit their harmful secretions to combat aging and disease.
Area of Science:
- Gerontology and Cellular Biology
- Molecular Biology and Immunology
Background:
- Cellular senescence is a fundamental aging process with dual roles, impacting development, tumor suppression, and organismal health.
- Senescent cells can exert beneficial effects acutely but become detrimental chronically, promoting inflammation and cancer via the senescence-associated secretory phenotype (SASP).
Purpose of the Study:
- To review current therapeutic strategies targeting cellular senescence for aging-related diseases and cancer.
- To discuss the advantages and disadvantages of senolytic, SASP inhibition, and immune-enhancement therapies.
Main Methods:
- Literature review of cellular senescence mechanisms and therapeutic interventions.
- Analysis of the impact of senescent cell persistence on organismal health.
- Discussion of senolytic, SASP inhibition, and immunosurveillance strategies.
Main Results:
- Short-term senescent cells aid tissue repair, while long-term cells promote chronic disease through SASP.
- Therapeutic approaches include senolytics, SASP inhibitors, and enhancing immunosurveillance.
- Cancer therapies may induce senescence but require clearance of senescent-like cells to prevent pro-tumorigenic states.
Conclusions:
- Targeting cellular senescence offers promising avenues for treating age-related diseases.
- Balancing the transient benefits of senescence with the risks of chronic SASP is crucial for therapeutic success.
- Further research is needed to optimize therapies that selectively eliminate harmful senescent cells or mitigate their effects.
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