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Coenzyme Q 10 (CoQ 10 ) 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 10 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 10 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 10 in skin ageing. The present study aimed to compare the bioavailability of exogenously added CoQ 10 , in the form of ubiquinone or ubiquinol, to CoQ 10 -deprived HDF, and to determine their efficacy in rescuing the senescent phenotype induced by CoQ 10 deprivation. First, additional senescence markers were implemented to further support the pro-ageing effect of statin-induced CoQ 10 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 10 supplementation to statin-treated HDF was able to counteract CoQ 10 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 10 for skin vitality and strongly support the use of both forms as a beneficial and effective anti-ageing skin care treatment., (Copyright © 2021. Published by Elsevier Inc.)

Coenzyme Q 10 (CoQ 10 ) is an endogenous lipophilic quinone, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the aging process. In fact, coenzyme Q 10 synthesis is known to decrease with age in different tissues including skin. Moreover, synthesis can be inhibited by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins, that are widely used hypocholesterolemic drugs. They target a key enzymatic step along the mevalonate pathway, involved in the synthesis of both cholesterol and isoprenylated compounds including CoQ 10 .In the present study, we show that pharmacological CoQ 10 deprivation at concentrations of statins > 10000 nM triggers intracellular oxidative stress, mitochondrial dysfunction and generates cell death in human dermal fibroblasts (HDF). On the contrary, at lower statin concentrations, cells and mainly mitochondria, are able to partially adapt and prevent oxidative imbalance and overt mitochondrial toxicity. Importantly, our data demonstrate that CoQ 10 decrease promotes mitochondrial permeability transition and bioenergetic dysfunction leading to premature aging of human dermal fibroblasts in vitro .

Background: Periostin is a secreted 90kDa matricellular protein, which is predominantly expressed in collagen-rich tissues. Collagen is the most abundant protein in mammals and has great tensile strength. Recent investigations have shown that periostin influences collagen fibrillogenesis and biomechanical properties of murine connective tissues., Objective: We investigated the function of periostin concerning collagen homeostasis during intrinsic and extrinsic skin aging. For this purpose, human skin samples of young and old donors as well as samples of photoaged and sun-protected skin areas were analyzed for periostin expression. Using in vitro models, we determined the cell types responsible for periostin expression and performed functional analyses with periostin knockdown cells., Methods: TaqMan Real-Time PCR, UV irradiation, knockdown experiments, immunostaining, electron microscopy, collagen degradation assay, collagen crosslink analysis., Results: Periostin expression is highest in the papillary dermis and downregulated during skin aging. Fibroblasts and non-follicular skin derived precursors were identified as main source for periostin expression in human skin. Periostin knockdown in fibroblasts has no effect on collagen expression, but results in an increased fibril diameter and aberrant collagen structure. This leads to an increased susceptibility of collagen toward proteases, whereas recombinant periostin protects collagen fibrils from degradation., Conclusion: Our data show that periostin plays an important role for proper collagen assembly and homeostasis. During skin aging periostin expression decreases and contributes to the phenotype of aged skin., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)