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SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Senopathies-Diseases Associated with Cellular Senescence
Oleh Lushchak1,2,3, Markus Schosserer4,5, Johannes Grillari1,5,6
1Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria.
Abstract:
Cellular senescence describes a stable cell cycle arrest state with a characteristic phenotype. Senescent cells accumulate in the human body during normal aging, limiting the lifespan and promoting aging-related, but also several non-related, pathologies. We propose to refer to all diseases whose pathogenesis or progression is associated with cellular senescence as "senopathies". Targeting senescent cells with senolytics or senomorphics is likely to mitigate these pathologies. Examples of senopathies include cardiovascular, metabolic, musculoskeletal, liver, kidney, and lung diseases and neurodegeneration. For all these pathologies, animal studies provide clear mechanistic evidence for a connection between senescent cell accumulation and disease progression. The major persisting challenge in developing novel senotherapies is the heterogeneity of senescence phenotypes, causing a lack of universal biomarkers and difficulties in discriminating senescent from non-senescent cells.
Insights
Cellular senescence, a state of cell cycle arrest, contributes to aging and disease. Targeting these senescent cells offers a promising therapeutic strategy for various "senopathies".
Area of Science:
- Gerontology and Cellular Biology
- Pathology and Disease Mechanisms
Background:
- Cellular senescence is a stable cell cycle arrest state with a distinct phenotype.
- Accumulation of senescent cells in the body during aging contributes to age-related diseases and pathologies.
- These senescent cells play a role in aging and various diseases, impacting lifespan and health.
Purpose of the Study:
- To introduce the term "senopathies" for diseases associated with cellular senescence.
- To highlight the therapeutic potential of targeting senescent cells (senolytics and senomorphics) for disease mitigation.
- To underscore the challenges in senotherapy development due to senescence heterogeneity.
Main Methods:
- Review of existing literature on cellular senescence and its role in disease.
- Identification and categorization of diseases linked to senescent cell accumulation.
- Analysis of evidence from animal studies demonstrating the connection between senescent cells and disease progression.
Main Results:
- Cellular senescence is implicated in a wide range of pathologies, including cardiovascular, metabolic, musculoskeletal, liver, kidney, lung diseases, and neurodegeneration.
- Animal studies provide strong mechanistic evidence linking senescent cell accumulation to disease progression.
- The heterogeneity of senescence phenotypes presents a significant challenge for developing universal biomarkers and effective senotherapies.
Conclusions:
- Cellular senescence is a key driver in the pathogenesis and progression of numerous diseases, now termed "senopathies".
- Targeting senescent cells holds significant therapeutic promise for mitigating a broad spectrum of age-related and other pathologies.
- Overcoming the heterogeneity of senescence is crucial for advancing senotherapies and developing effective treatments.
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