Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence

Abstract 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 s...

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Autores principales:	Elena Zoico, Nicole Nori, Elena Darra, Maela Tebon, Vanni Rizzatti, Gabriella Policastro, Annamaria De Caro, Andrea Petronio Rossi, Francesco Fantin, Mauro Zamboni
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fba4af90daf6415bbf12b0f926426076
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spelling	oai:doaj.org-article:fba4af90daf6415bbf12b0f9264260762021-12-05T12:12:50ZSenolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence10.1038/s41598-021-02544-02045-2322https://doaj.org/article/fba4af90daf6415bbf12b0f9264260762021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02544-0https://doaj.org/toc/2045-2322Abstract 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 (H2O2) 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. H2O2 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.Elena ZoicoNicole NoriElena DarraMaela TebonVanni RizzattiGabriella PolicastroAnnamaria De CaroAndrea Petronio RossiFrancesco FantinMauro ZamboniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elena Zoico Nicole Nori Elena Darra Maela Tebon Vanni Rizzatti Gabriella Policastro Annamaria De Caro Andrea Petronio Rossi Francesco Fantin Mauro Zamboni Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
description	Abstract 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 (H2O2) 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. H2O2 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.
format	article
author	Elena Zoico Nicole Nori Elena Darra Maela Tebon Vanni Rizzatti Gabriella Policastro Annamaria De Caro Andrea Petronio Rossi Francesco Fantin Mauro Zamboni
author_facet	Elena Zoico Nicole Nori Elena Darra Maela Tebon Vanni Rizzatti Gabriella Policastro Annamaria De Caro Andrea Petronio Rossi Francesco Fantin Mauro Zamboni
author_sort	Elena Zoico
title	Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
title_short	Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
title_full	Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
title_fullStr	Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
title_full_unstemmed	Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
title_sort	senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fba4af90daf6415bbf12b0f926426076
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Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence

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