TBHP treatment as a model for cellular senescence and pollution-induced skin aging. (September 2020)

• Record Type: Journal Article
• Authors: Wedel, Sophia; Martic, Ines; Hrapovic, Nina; Fabre, Susanne; Madreiter-Sokolowski, Corina T.; Haller, Thomas; Pierer, Gerhard; Ploner, Christian; Jansen-Dürr, Pidder; Cavinato, Maria
• Is Part Of: Mechanisms of ageing and development. Volume 190(2020)
• Publication Date: 2020-09
• Subjects: cPDL cumulative Population Doublings -- D1 Day One -- DAPI 4′, 6-diamidino-2-phenylindole -- ΔΨM Mitochondrial Membrane Potential, DHE, Dihydroethidium -- DMEM Dulbecco's Modified Eagle's Medium -- DPBS Dulbecco's Phosphate Buffered Saline -- EDTA Ethylenediaminetetraacetic acid, FCCP, Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone -- GAD_Disease 'Aging' Genetic Association Database Correlated with Aging -- GAPDH Glyceraldehyde 3-phosphate dehydrogenase -- H&E Hematoxylin and Eosin Staining -- HFF-1 Human Foreskin Fibroblasts -- HSDF Human Skin Dermal Fibroblasts -- HSEK Human Skin Epidermal Keratinocytes -- MMPs Matrix metalloproteases -- mtDNA mitochondrial DNA -- nDNA nuclear DNA -- PBS Phosphate Buffered Saline -- RIPA Radioimmunoprecipitation Assay -- RNAseq RNA Sequencing -- ROS Reactive Oxygen Species -- SASP Senescence-associated Secretory Phenotype -- SA-β-galactosidase Senescence-associated β-galactosidase -- SD Standard Deviation -- tBHP tert-butyl hydroperoxide; oxidative stress -- cigarette smoke -- epidermal thinning -- collagen degradation; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2020.111318
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: tBHP treatment induces premature cellular senescence in skin fibroblasts. Oxidative stress-induced mitochondrial damage is a characteristic of tBHP-induced senescence. In 3D reconstructed skin, tBHP treatment induces epidermal thinning. tBHP treatment of ex vivo skin results in a reduction of collagen fiber thickness. Abstract: Accumulation of senescent cells promotes the development of age-related pathologies and deterioration. In human skin, senescent cells potentially impair structure and function by secreting a mixture of signaling molecules and proteases that influence neighboring cells and degrade extracellular matrix components, such as elastin and collagen. One of the key underlying mechanisms of senescence and extrinsic skin aging is the increase of intracellular reactive oxygen species and resulting oxidative stress. Tert-butyl hydroperoxide (tBHP) is a known inducer of oxidative stress and cellular damage, acting at least in part by depleting the antioxidant glutathione. Here, we provide a detailed characterization of tBHP-induced senescence in human dermal fibroblasts in monolayer culture. In addition, results obtained with more physiological experimental models revealed that tBHP treated 3D reconstructed skin and ex vivo skin developed signs of chronic tissue damage, displaying reduced epidermal thickness and collagen fiber thinning. We, therefore, propose that tBHP treatment can be used as a model to study the effects of extrinsic skin aging, focusing mainly on the influence of environmental pollution.