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Targeting cellular senescence in metabolic disease
Allyson K Palmer1, Tamar Tchkonia2, James L Kirkland3
1Division of Hospital Internal Medicine, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA; Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
Molecular Metabolism
|September 18, 2022
Summary
Cellular senescence, a state of cell cycle arrest, contributes to inflammation and metabolic dysfunction. Targeting senescent cells with novel therapies like senolytics shows promise for treating age-related and obesity-related diseases.
Area of Science:
- Cellular and Molecular Biology
- Immunology
- Metabolic Diseases
Background:
- Cellular senescence is characterized by cell cycle arrest, apoptosis resistance, and a pro-inflammatory secretome.
- Accumulation of senescent cells in tissues like adipose, brain, kidney, pancreas, and liver is linked to aging and obesity.
- Senescent cells perpetuate inflammation and contribute to metabolic dysfunction, with impaired immune clearance in aging and obesity.
Purpose of the Study:
- To explore the role of cellular senescence in metabolic dysfunction.
- To review the therapeutic potential of targeting senescent cells and their products.
Main Methods:
- Review of literature on cellular senescence, aging, obesity, and metabolic dysfunction.
- Analysis of current and emerging therapeutic strategies targeting senescent cells, including senolytics and immune-based approaches.
Main Results:
- Senescent cells and their secretome promote inflammation and metabolic dysfunction.
- Impaired immune clearance of senescent cells in aging and obesity exacerbates these effects.
- Targeting senescent cells improves metabolic function in aging and obesity models.
- Senolytic drugs show early promise in depleting senescent cells in human clinical trials.
Conclusions:
- Senescence-targeting therapeutics, including senolytics and enhanced immune clearance, offer significant potential for treating metabolic dysfunction.
- These strategies hold promise for various diseases associated with aging and obesity.
- Further investigation and clinical trials are warranted to fully establish the efficacy of these novel therapeutics.
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