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Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Translating cellular senescence research into clinical practice for metabolic disease
Selim Chaib1,2, Allyson K Palmer3,4, Saranya P Wyles5
1Center for Advanced Gerotherapeutics, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Abstract:
Translational research on cellular senescence has led to numerous early-phase clinical trials targeting senescent cells to treat, prevent or alleviate multiple disorders and diseases, including metabolic diseases and their comorbidities. Cellular senescence is a cell fate that occurs in response to stressors, including metabolic disruptions, and is one of the hallmarks (or pillars) of ageing. In their senescent state, cells cease proliferation and can develop a senescence-associated secretory and metabolic phenotype that contributes to the pathogenesis of metabolic dysfunction associated with obesity and ageing. Metabolic stress, which is central to the development of metabolic diseases, can trigger cellular senescence, thereby enabling a vicious cycle that exacerbates metabolic dysfunction. Therapies targeting senescent cells (senotherapeutics), either alone or in combination with other gerotherapies or lifestyle interventions, hold great promise for addressing the ongoing obesity epidemic and the need for improved therapies to prevent and treat metabolic diseases and their complications and comorbidities. In this Review, we discuss novel senotherapeutics, including challenges related to the translation of these therapies and the need to establish gerodiagnostic biomarkers to track the elimination of senescent cells, define eligibility and measure efficacy, as well as considerations for clinical trial design and execution.
Insights
Targeting cellular senescence, a hallmark of aging, shows promise for treating metabolic diseases. Senotherapeutics offer potential to combat obesity and related complications by clearing senescent cells.
Area of Science:
- Gerontology
- Metabolic Diseases
- Cellular Biology
Background:
- Cellular senescence is a key aging hallmark triggered by stressors like metabolic disruptions.
- Senescent cells exhibit a secretory phenotype contributing to metabolic dysfunction in obesity and aging.
- Metabolic stress exacerbates dysfunction by inducing cellular senescence, creating a detrimental cycle.
Purpose of the Study:
- To review novel senotherapeutics for treating metabolic diseases and their comorbidities.
- To discuss challenges in translating senotherapeutic therapies into clinical practice.
- To highlight the need for gerodiagnostic biomarkers for senescent cell elimination and treatment efficacy.
Main Methods:
- Review of current translational research on senotherapeutics.
- Analysis of challenges in clinical trial design for senotherapies.
- Discussion on the role of gerodiagnostic biomarkers in senolytic therapy.
Main Results:
- Senotherapeutics demonstrate potential in early-phase clinical trials for various disorders.
- Targeting senescent cells offers a promising strategy against the obesity epidemic.
- Effective senotherapeutics require robust biomarkers for tracking efficacy and patient eligibility.
Conclusions:
- Senotherapeutics hold significant promise for preventing and treating metabolic diseases, obesity, and aging-related complications.
- Overcoming translational challenges and developing reliable gerodiagnostic biomarkers are crucial for clinical success.
- Combination therapies and optimized clinical trial designs are essential for advancing senotherapeutics.
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