Sirtuin expression in skin fibroblasts: pharmacomodulatory effect of quercetin

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Introduction. Sirtuins (SIRTs) are NAD+-dependent histone deacetylases involved in the intracellular regulation of multiple biological processes including DNA repair, autophagy, inflammation, oxidative stress defence and metabolism associated with age-associated diseases, including dermal ageing. Reduced levels of these proteins in tissues correlate with the progression of endothelial dysfunction and cellular aging, which makes sirtuins promising targets for the prevention and therapy of age-related pathologies. The development of strategies to activate the expression of SIRT -1, -3, -6 in cells to inhibit the aging process is relevant. The natural flavonoid quercetin, a natural flavonoid with proven geroprotective efficacy, is capable of influencing sirtuin gene expression.

Purpose. To study the modulatory effect of quercetin in the hyaluronan gel on the content of endogenous geroprotective proteins SIRT -1, -3, -6 in human skin fibroblast culture during the development of inflammaging.

Material and methods. The study was carried out on cell cultures of human skin fibroblasts with modelling of genotoxic stress inflammaging by UV-irradiation. 1 ml of hydrogel preparation with quercetin was injected into growth cultures, obtaining 3 groups of cells under study. Methods of immunocytochemistry and immunofluorescence confocal microscopy were applied to visualise the content of sirtuins in them. The obtained images were analysed using ImageJ software. Relative area of expression was calculated as the area of marker expression to the total area of the field of view. Statistical processing was performed in Origin.

Results. Revitalisant containing hyaluronan and quercetin showed effective enhancement of SIRT-1, -3, -6 levels in senescent skin cells.

Conclusion. Quercetin, an activator of SIRT-1, -3, -6 dermal anti-aging biomarkers, has therapeutic potential in the treatment of age-related pathologies. Selective pharmacological modulation of sirtuin activity in skin fibroblasts by quercetin appears to be an effective and promising way to slow down dermal aging.

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作者简介

Anna Kosova

Saint-Petersburg Research Institute of Phthisiopulmonology; ITMO University

编辑信件的主要联系方式.
Email: annkosova@bk.ru
ORCID iD: 0009-0003-1893-4733
SPIN 代码: 4202-0293

research laboratory assistant of the Research Laboratory of Molecular Neuroimmunoendocrinology, Department of Translational Biomedicine, student

俄罗斯联邦, Ligovsky Prospekt, b. 2–4, Saint-Petersburg, 191036; Kronverksky pr. 49, lit. A, Saint-Petersburg, 197101

Ekaterina Mironova

Saint-Petersburg Research Institute of Phthisiopulmonology; ITMO University; Saint Petersburg Institute of bioregulation and gerontology; Saint-Petersburg State University

Email: katrine1994@mail.ru
ORCID iD: 0000-0001-8134-5104
SPIN 代码: 5992-1419

Head of the Research Laboratory of Molecular Neuroimmunoendocrinology, Department of Translational Biomedicine, practice teacher, Head of the Laboratory of Molecular Biology of the Cell, teacher

俄罗斯联邦, Ligovsky Prospekt, b. 2–4, Saint-Petersburg, 191036; Kronverksky pr. 49, lit. A, Saint-Petersburg, 197101; Dinamo Ave, 3, Saint-Petersburg, 197110; Universitetskaya amb. 7–9, Saint-Petersburg, 199034

Yulia Belova

Saint-Petersburg Research Institute of Phthisiopulmonology; Saint Petersburg Institute of bioregulation and gerontology

Email: bi.day.eddie@gmail.com
ORCID iD: 0009-0007-0961-3515
SPIN 代码: 7197-4731

research laboratory assistant of the Research Laboratory of Molecular Pathology, Department of Translational Biomedicine, Researcher at the Laboratory of Functional Morphology

俄罗斯联邦, Ligovsky Prospekt, b. 2–4, Saint-Petersburg, 191036; Dinamo Ave, 3, Saint-Petersburg, 197110

Anna Drobintseva

Saint-Petersburg Research Institute of Phthisiopulmonology; Saint-Petersburg State Pediatric Medical University

Email: anna.drobintseva@gmail.com
ORCID iD: 0000-0002-6833-6243
SPIN 代码: 4277-0122

Senior Researcher of the Research Laboratory of Molecular Neuroimmunoendocrinology, Department of Translational Biomedicine, Head of the Department of Histology and Embryology named after Prof. A.G. Knorre

俄罗斯联邦, Ligovsky Prospekt, b. 2–4, Saint-Petersburg, 191036; Litovskaya St., 2, Saint-Petersburg, 194100

Vladimir Khabarov

Hyaluronic Acid Research Center

Email: px716@mail.ru
ORCID iD: 0000-0002-4138-4835
SPIN 代码: 2784-9748

director, PhD

俄罗斯联邦, Komsomolsky pr., 38/16, Moscow, 119146

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2. Fig. 1. Expression of SIRTs 1 and 3 in human skin fibroblast culture during the development of inflammaging. Note. Immunofluorescence staining with antibodies to: a – SIRT1 (green glow, Alexa 488), б – SIRT3 (red glow, Alexa 647). Cell nuclei stained with blue (DAPI). Magnification: ×1000.

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3. Fig. 2. Expression of SIRT6 in human skin fibroblast culture during the development of inflammaging. Immunofluorescence staining with antibodies to SIRT6 (green glow, Alexa 488). Cell nuclei stained with blue (DAPI). Magnification: ×1000 Note. a – control, б – Inflammaging, в – Inflammaging + quercetin + hyaluronan.

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4. Fig. 3. Expression of SIRT-1, -3, -6 proteins in human skin fibroblasts in control culture, during the development of inflammaging and under the influence of hyaluronan preparation with quercetin Note. * – statistically significant differences from the “control” group (p<0.05), ** – statistically significant differences from the “inflammaging” group (p<0.05).

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