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Updated: Jul 2, 2026
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Senescent cell depletion alleviates obesity-related metabolic and cardiac disorders
Tábatha de Oliveira Silva1, Guilherme Lunardon2, Caroline A Lino2
1Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil; Center for Regenerative Medicine, USF Health Heart Institute, University of South Florida, Tampa, FL, USA.
Abstract:
Obesity is a major contributor to metabolic and cardiovascular disease. Although senescent cells have been shown to accumulate in adipose tissue, the role of senescence in obesity-induced metabolic disorders and in cardiac dysfunction is not yet clear; therefore, the therapeutic potential of managing senescence in obesity-related metabolic and cardiac disorders remains to be fully defined.
Objective:
We investigated the beneficial effects of a senolytic cocktail (dasatinib and quercetin) on senescence and its influence on obesity-related parameters.
Methods And Results:
We found that the increase in body weight and adiposity, glucose intolerance, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic disorders which were induced by an obesogenic diet were alleviated by senolytic cocktail treatment in mice. Treatment with senolytic compounds eliminated senescent cells, counteracting the activation of the senescence program and DNA damage in white adipose tissue (WAT) observed with an obesogenic diet. Moreover, the senolytic cocktail prevented the brown adipose tissue (BAT) whitening and increased the expression of the thermogenic gene profile in BAT and pWAT. In the hearts of obese mice, senolytic combination abolished myocardial maladaptation, reducing the senescence-associated secretory phenotype (SASP) and DNA damage, repressing cardiac hypertrophy, and improving diastolic dysfunction. Additionally, we showed that treatment with the senolytic cocktail corrected gene expression programs associated with fatty acid metabolism, oxidative phosphorylation, the P53 pathway, and DNA repair, which were all downregulated in obese mice.
Conclusions:
Collectively, these data suggest that a senolytic cocktail can prevent the activation of the senescence program in the heart and WAT and activate the thermogenic program in BAT. Our results suggest that targeting senescent cells may be a novel therapeutic strategy for alleviating obesity-related metabolic and cardiac disorders.
Insights
Senolytic cocktail treatment reversed obesity-induced metabolic and cardiac issues in mice by clearing senescent cells. This approach shows promise for treating obesity-related disorders.
Area of Science:
- Cellular senescence
- Metabolic disorders
- Cardiovascular disease
Background:
- Obesity is a significant risk factor for metabolic and cardiovascular diseases.
- Senescent cells accumulate in adipose tissue, but their role in obesity-related complications is unclear.
- Therapeutic strategies targeting senescence in obesity are not fully defined.
Purpose of the Study:
- Investigate the effects of a senolytic cocktail (dasatinib and quercetin) on obesity-related parameters.
- Determine the impact of senolytics on senescence and metabolic dysfunction in diet-induced obesity.
Main Methods:
- Administered a senolytic cocktail (dasatinib and quercetin) to mice on an obesogenic diet.
- Assessed body weight, adiposity, glucose tolerance, insulin resistance, and lipid profiles.
- Analyzed senescent cell markers, DNA damage, and gene expression in white adipose tissue (WAT), brown adipose tissue (BAT), and cardiac tissue.
Main Results:
- Senolytic treatment alleviated obesity-induced weight gain, adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hepatic disorders.
- Senolytics cleared senescent cells and DNA damage in WAT, preventing BAT whitening and enhancing thermogenic gene expression.
- Cardiac function improved, with reduced myocardial maladaptation, SASP, DNA damage, and hypertrophy.
Conclusions:
- Senolytic cocktail prevents senescence activation in the heart and WAT, and activates thermogenic programs in BAT.
- Targeting senescent cells represents a novel therapeutic strategy for obesity-related metabolic and cardiac disorders.
