Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
Open accessAbstract
The dysfunction of adipose tissue with aging and the accumulation of senescent cells has been implicated in the pathophysiology of chronic diseases. Recently interventions capable of reducing the burden of senescent cells and in particular the identification of a new class of drugs termed senolytics have been object of extensive investigation. We used an in vitro model of induced senescence by treating both pre-adipocytes as well as mature adipocytes with hydrogen peroxide (H 2 O 2 ) at a sub-lethal concentration for 3 h for three consecutive days, and hereafter with 20 uM quercetin at a dose that in preliminary experiments resulted to be senolytic without cytotoxicity. H 2 O 2 treated pre-adipocytes and adipocytes showed typical senescence-associated features including increased beta-galactosidase activity (SA-ß-gal) and p21, activation of ROS and increased expression of pro-inflammatory cytokines. The treatment with quercetin in senescent pre-adipocytes and adipocytes was associated to a significant decrease in the number of the SA-β-gal positive cells along with the suppression of ROS and of inflammatory cytokines. Besides, quercetin treatment decreased miR-155-5p expression in both models, with down-regulation of p65 and a trend toward an up-regulation of SIRT-1 in complete cell extracts. The senolytic compound quercetin could affect AT ageing by reducing senescence, induced in our in vitro model by oxidative stress. The downregulation of miRNA-155-5p, possibly through the modulation of NF-κB and SIRT-1, could have a key role in the effects of quercetin on both pre-adipocytes and adipocytes.
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Hydrogen peroxide-induced senescence also triggers inflammation, characterized by the upregulation of pro-inflammatory cytokines such as IL-6, TNF-α, and MCP-1.
“Hydrogen peroxide-induced senescence also triggers inflammation, characterized by the upregulation of pro-inflammatory cytokines such as IL-6, TNF-α, and MCP-1.282,283”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [283]
Treatment with quercetin significantly lowers levels of ROS and inflammatory cytokines, reduces expression of SA-β gal, p16 and p53, and markedly increases that of antioxidant enzymes SOD and CAT, regardless of the type of oxidative trigger used to induce senescence.
“Results obtained on different cell lines show that treatment with quercetin significantly lowers the levels of ROS and inflammatory cytokines, reduces the expression of SA-β gal, p16 and p53 and markedly increases that of the antioxidant enzymes SOD and CAT, regardless of the type of oxidative trigger used to induce senescence [258,259,260,261,262].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [262]
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We are all aging, and here's why
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Body Composition and Senescence: Impact of Polyphenols on Aging-Associated Events
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Sauchinone Ameliorates Senescence Through Reducing Mitochondrial ROS Production
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High copper levels induce premature senescence in 3T3-L1 preadipocytes
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Senolytic treatment induces oligodendrocyte dysfunction and demyelination in the corpus callosum
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Examining the Effects of Quercetin on Phenotypic Characteristics of Human Mesenchymal Stem Cells
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Cross-talk between aging resilience pathways and autoimmunity onset
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In vitro senescence and senolytic functional assays
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Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics
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Effects of Chlorogenic Acid on Cellular Senescence in an In Vitro Model of 3T3-L1 Murine Adipocytes
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Natural Product-Derived Senotherapeutics: Extraction and Biological Evaluation Techniques
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BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS
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Cellular Senescence in Cancer: Mechanisms, Roles in Tumor Progression, and Therapeutic Implications
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Poly-L-Lactic Acid Filler Increases Adipogenesis and Adiponectin in Aged Subcutaneous Tissue
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Comparative analysis of various senescence inducers in proximal renal tubular cells
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Integrating clinical evidence with natural product therapies for elderly-onset type 2 diabetes
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Quercetin rejuvenates aged adipose progenitor cells by attenuating inflammatory pathways
Fan, J., Zhou, L. Y., Song, R., Yang, Y., Geng, Y., Zhang, X., Yu, Q., Li, Z., Wang, Y., & He, W. (2026) · Experimental Gerontology · doi:10.1016/j.exger.2026.113027 · Cited by 2 · see citing works
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ε-Viniferin Rejuvenates Senescence via RGS16 Regulation: In Vitro Evidence
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Adipose Tissue Aging and Natural Interventions: Potential Roles of Polyphenols and Polysaccharides
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Quercetin Mitigates Oxidative Stress-Induced Premature Senescence in SH-SY5Y Neuronal-like Cells
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Microrna-155 as a Possible Pharmacological Target
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Boiogito Ameliorates Hydrogen Peroxide-Induced Impairment of Glucose Uptake in 3T3-L1 Adipocytes
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- Authors
- Zoico, E., Nori, N., Darra, E., Tebon, M., Rizzatti, V., Policastro, G., De Caro, A., Rossi, A. P., Fantin, F., & Zamboni, M.
- Affiliations
- University of Verona (IT)
- Corresponding author
- Zoico, Elena
- Venue
- Scientific Reports
- Published
- 2021-12-01
- Volume
- 11
- Issue
- 1
- Pages
- 23237-23237
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8636588
- OpenAlex
- W3215963477
- Cited by
- 94
- References
- 55
- Citations by year
- 2026: 25 · 2025: 17 · 2024: 25 · 2023: 18 · 2022: 9
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- fondazione cariplo
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- quercetin, senolytics, cellular senescence, adipocytes, preadipocytes, hydrogen peroxide-induced senescence, oxidative stress, senescence-associated β-galactosidase, reactive oxygen species, inflammatory cytokines, miR-155-5p, NF-κB, SIRT1, senolytic therapy
- MeSH terms
- Senotherapeutics, Aging, Animals, Hydrogen Peroxide, Quercetin, Cellular Senescence, Adipocytes, Oxidative Stress, MicroRNAs, 3T3-L1 Cells, Mice
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