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泛醌和还原型泛醌在人真皮成纤维细胞衰老模型中的抗衰老作用。

Anti-ageing effects of ubiquinone and ubiquinol in a senescence model of human dermal fibroblasts.

机构信息

Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, Ancona, I-60131, Italy.

Research and Development, Beiersdorf AG, Unnastrasse 48, Hamburg, 20245, Germany.

出版信息

Free Radic Biol Med. 2021 Mar;165:282-288. doi: 10.1016/j.freeradbiomed.2021.01.032. Epub 2021 Jan 19.


DOI:10.1016/j.freeradbiomed.2021.01.032
PMID:33482334
Abstract

Coenzyme Q (CoQ) is an endogenous lipophilic quinone found in equilibrium between its oxidised (ubiquinone) and reduced (ubiquinol) form, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the ageing process. CoQ biosynthesis decreases with age in different tissues including skin and its biosynthesis can be modulated by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins. Statin-induced CoQ deprivation has previously been shown to be associated with the development of a senescence phenotype in cultured human dermal fibroblasts (HDF), hence this model was used to further investigate the role of CoQ in skin ageing. The present study aimed to compare the bioavailability of exogenously added CoQ, in the form of ubiquinone or ubiquinol, to CoQ-deprived HDF, and to determine their efficacy in rescuing the senescent phenotype induced by CoQ deprivation. First, additional senescence markers were implemented to further support the pro-ageing effect of statin-induced CoQ deprivation in HDF. Indeed, numerous senescence-associated secretory phenotype (SASP) markers such as p21, IL-8, CXCL1, and MMP-1 were upregulated, whereas components of the extracellular matrix were downregulated (elastin, collagen type 1). Next, we showed that CoQ supplementation to statin-treated HDF was able to counteract CoQ deprivation and rescued the development of selected senescence/ageing markers in HDF. Ubiquinol resulted more bioavailable than ubiquinone at the same concentration (15 μg/mL) and it significantly improved the cellular oxidative status even within isolated mitochondria highlighting an effective subcellular delivery. Ubiquinol was also more efficient compared to ubiquinone in reverting the expression of the senescent phenotype, quantified in terms of β-galactosidase positivity, p21, collagen type 1, and elastin at the gene and protein expression levels. In conclusion, our results highlight the pivotal role of CoQ for skin vitality and strongly support the use of both forms as a beneficial and effective anti-ageing skin care treatment.

摘要

辅酶 Q(CoQ)是一种内源性亲脂性醌,存在于其氧化(泛醌)和还原(泛醇)形式之间的平衡中,广泛存在于生物膜中,具有抗氧化和生物能量特性,这两者对衰老过程都至关重要。CoQ 的生物合成在不同组织中随年龄的增长而减少,包括皮肤,其生物合成可以通过 3-羟基-3-甲基戊二酰基辅酶 A(HMG-CoA)还原酶抑制剂(如他汀类药物)进行调节。先前已经表明,他汀类药物诱导的 CoQ 缺乏与培养的人真皮成纤维细胞(HDF)衰老表型的发展有关,因此该模型被用于进一步研究 CoQ 在皮肤衰老中的作用。本研究旨在比较外源性添加的 CoQ(泛醌或泛醇形式)对 CoQ 缺乏的 HDF 的生物利用度,并确定它们在挽救 CoQ 缺乏诱导的衰老表型方面的功效。首先,实施了其他衰老标志物以进一步支持他汀类药物诱导的 CoQ 缺乏对 HDF 的促衰老作用。事实上,许多衰老相关分泌表型(SASP)标志物,如 p21、IL-8、CXCL1 和 MMP-1 上调,而细胞外基质的成分下调(弹性蛋白、胶原蛋白 1)。接下来,我们表明,向他汀类药物处理的 HDF 中补充 CoQ 能够抵消 CoQ 缺乏,并挽救 HDF 中选定的衰老/老化标志物的发展。与相同浓度(15μg/mL)的泛醌相比,泛醇更具生物利用度,即使在分离的线粒体中,它也能显著改善细胞氧化状态,突出了有效的亚细胞递送。与泛醌相比,泛醇在逆转衰老表型的表达方面也更有效,根据β-半乳糖苷酶阳性、p21、胶原蛋白 1 和弹性蛋白的基因和蛋白表达水平进行量化。总之,我们的结果强调了 CoQ 对皮肤活力的关键作用,并强烈支持使用这两种形式作为有益和有效的抗衰老皮肤护理治疗。

相似文献

[1]
Anti-ageing effects of ubiquinone and ubiquinol in a senescence model of human dermal fibroblasts.

Free Radic Biol Med. 2021-3

[2]
Modulation of Coenzyme Q content and oxidative status in human dermal fibroblasts using HMG-CoA reductase inhibitor over a broad range of concentrations. From mitohormesis to mitochondrial dysfunction and accelerated aging.

Aging (Albany NY). 2019-5-10

[3]
Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men.

Food Funct. 2018-11-14

[4]
Bioenergetic and antioxidant properties of coenzyme Q10: recent developments.

Mol Biotechnol. 2007-9

[5]
Combining Ubiquinol With a Statin May Benefit Hypercholesterolaemic Patients With Chronic Heart Failure.

Heart Lung Circ. 2019-9-20

[6]
Modulation of Oxidative Status by Normoxia and Hypoxia on Cultures of Human Dermal Fibroblasts: How Does It Affect Cell Aging?

Oxid Med Cell Longev. 2018-9-23

[7]
Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ deficiency.

Biochim Biophys Acta. 2014-7

[8]
Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals.

Nutrients. 2020-3-16

[9]
Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA.

Biofactors. 2003

[10]
The Influence of Atorvastatin, Amlodipine and Ethoxidol on Ubiquinol and Ubiquinone Endogenous Plasma Concentrations in Patients with Chronic Heart Failure.

Curr Drug Metab. 2023

引用本文的文献

[1]
Coenzyme Q10 protects keratinocytes against oxidation-induced energy stress as revealed by spatiotemporal analysis of cell energetics.

Sci Rep. 2025-4-25

[2]
Extract Modulates Gene Expression Profiles Associated with Antioxidant Defense, Cytoprotection, and Senescence in Human Dermal Fibroblasts: Investigation of Quantitative Gene Expression by qPCR.

Curr Issues Mol Biol. 2025-2-18

[3]
Supplementation with aspalathin and sulforaphane protects cultured cardiac cells against dyslipidemia-associated oxidative damage.

Metabol Open. 2025-1-3

[4]
Preparation and Evaluation of Complexed Ubiquinone (Coenzyme Q10) Antiaging Hyaluronic Acid-Vitamin C Serum for Skin Care.

J Cosmet Dermatol. 2025-1

[5]
Rediscovering the chemistry of the species: potential fungi for metabolites and enzymes of biological, industrial, and environmental values.

RSC Adv. 2024-12-5

[6]
Superior Anti-arrhythmogenic Effect of Combined Conditioning with Nicotinamide Mononucleotide and Ubiquinol in Myocardial Ischemia/Reperfusion Injury in Aged Rats.

Adv Pharm Bull. 2024-10

[7]
T-Cell Senescence in Human Metabolic Diseases.

Diabetes Metab J. 2024-9

[8]
The Role of Coenzyme Q10 in Skin Aging and Opportunities for Topical Intervention: A Review.

J Clin Aesthet Dermatol. 2024-8

[9]
Elastogenesis in Focus: Navigating Elastic Fibers Synthesis for Advanced Dermal Biomaterial Formulation.

Adv Healthc Mater. 2024-10

[10]
MiR-17-5p-engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21.

Adv Sci (Weinh). 2024-4

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