The effect of degeneration of elastic fibres on loss of elasticity and wrinkle formation.

OBJECTIVE: Skin elasticity, which is vital for a youthful appearance, depends on the elastic fibres in the dermis. However, these fibres deteriorate with ageing, resulting in wrinkles and sagging. Changes that occur in the elastic fibres in living human skin and the relationship between elastic fibres and the state of the skin surface remain unclear. Therefore, it is necessary to verify the relationship between elastic fibres and skin elasticity. In this study, we investigated the association of the elastic fibre structure with skin elasticity and stratum corneum protein content in living human skin. METHODS: Thirty-five female volunteers aged 25-66 years were included in this study. Elastic fibres were observed using a multiphoton scanning laser biomicroscope. Skin elasticity was measured using a Cutometer, and stratum corneum proteins (Heat-shock protein 27 [HSP27] and galectin-7 [Gal-7]) in tape-stripped samples were analysed using an enzyme-linked immunosorbent assay. RESULTS: Elastic fibres exhibited increased curvature and thickness with increased age, with fragmentation observed in women aged >60 years. Elastin scores, which reflect thinness and curvature, were negatively correlated with age, whereas they were positively correlated with R7 elasticity (recovery ability). In individuals aged 20-30 years, higher levels of inflammatory markers (HSP27 and Gal-7) correlated with lower elastin scores; however, this trend was not observed in older participants. CONCLUSION: Elastic fibre deterioration worsened after 40 years of age, and this effect correlated with reduced skin recovery and increased wrinkles. In younger individuals, inflammatory markers affected elastic fibres. These findings can guide anti-ageing strategies that focus on elastic fibre preservation and inflammation control.

OBJECTIF: L'élasticité de la peau, vitale pour un aspect jeune, dépend des fibres élastiques du derme. Cependant, ces fibres se détériorent avec l'âge, ce qui entraîne des rides et un affaissement. Les changements qui se produisent dans les fibres élastiques de la peau humaine vivante et la relation entre les fibres élastiques et l'état de la surface de la peau restent peu clairs. Il est donc nécessaire de vérifier la relation entre les fibres élastiques et l'élasticité de la peau. Dans cette étude, nous avons étudié l'association de la structure des fibres élastiques avec l'élasticité de la peau et la teneur en protéine de la couche cornée dans une peau humaine vivante. MÉTHODES: 35 volontaires de sexe féminin âgés de 25 à 66 ans ont été inclus dans cette étude. Des fibres élastiques ont été observées à l'aide d'un biomicroscope à balayage laser multiphotonique. L'élasticité de la peau a été mesurée à l'aide d'un cutomètre, et les protéines de la couche cornée (les protéines de choc thermique 27 [Heat­shock protein 27, HSP27] et galectine­7 [Gal­7]) dans des échantillons avec bande adhésive ont été analysées à l'aide d'un dosage par la méthode immuno­enzymatique ELISA. RÉSULTATS: Les fibres élastiques présentaient une courbure et une épaisseur accrues avec l'âge, avec une fragmentation observée chez les femmes âgées de >60 ans. Les scores d'élastine, qui reflètent la minceur et la courbure, étaient corrélés négativement avec l'âge, tandis qu'ils étaient corrélés positivement avec l'élasticité de R7 (capacité de récupération). Chez les personnes âgées de 20 à 30 ans, des taux plus élevés de marqueurs inflammatoires (HSP27 et Gal­7) étaient corrélés avec une diminution des scores d'élastine; toutefois, cette tendance n'a pas été observée chez les participants plus âgés. CONCLUSION: La détérioration des fibres élastiques s'est aggravée après l'âge de 40 ans, et cet effet était corrélé à une récupération réduite de la peau et à une augmentation des rides. Chez les personnes plus jeunes, les marqueurs inflammatoires ont affecté les fibres élastiques. Ces résultats peuvent orienter les stratégies anti­âge qui se concentrent sur la préservation des fibres élastiques et le contrôle de l'inflammation.

Elastin microfibril interface-located protein 1 in fibroblasts is regulated by amphiregulin and interleukin-1α produced by keratinocytes.

OBJECTIVE: The structure of elastic fibres changes with ageing. Elastin microfibril interface-located protein 1 (EMILIN-1) is known to contribute to structural changes in elastic fibres. EMILIN-1 is one of the components of elastic fibres and also colocalizes with oxytalan fibres near the epidermis. Therefore, EMILIN-1 may be affected by epidermal-dermal interactions. The purpose of this study is to identify the key factors involved in epidermal-dermal interactions during the structural degeneration of elastic fibres. METHODS: Keratinocytes and fibroblasts were co-cultured, and changes in elastic fibre-related proteins were evaluated. Additionally, cytokine arrays were used to identify the factors involved in epidermal-dermal interactions. RESULTS: EMILIN-1 expression in fibroblasts was increased in the presence of keratinocytes, and its expression decreased when keratinocytes were stressed. Amphiregulin (AREG) and interleukin-1α (IL-1α) were identified as the keratinocyte-derived cytokines that influence the production of EMILIN-1, which is secreted by the fibroblasts. EMILIN-1 expression was promoted by AREG and decreased by IL-1α via an increase in cathepsin K (a catabolic enzyme). AREG and IL-1α were associated with changes in EMILIN-1 levels in fibroblasts. CONCLUSION: The findings suggest that the suppression of IL-1α expression and promotion of AREG expression in the epidermis could be a new approach that prevents the wrinkles and sagging caused by the structural changes in elastic fibres.

OBJECTIF: La structure des fibres élastiques change avec le vieillissement. La protéine située à l'interface des microfibrilles d'élastine 1 (EMILIN­1) est connue pour sa contribution aux changements structurels des fibres élastiques. EMILIN­1 est l'un des composants des fibres élastiques et colocalise également avec les fibres oxytalanes à proximité de l'épiderme. Par conséquent, EMILIN­1 peut être affectée par des interactions épidermiques­dermiques. Cette étude a objectif d'identifier les facteurs clés impliqués dans les interactions épidermiques­dermiques au cours de la dégénérescence structurelle des fibres élastiques. MÉTHODES: Co­cultiver les kératinocytes et les fibroblastes, et évaluer les changements dans les protéines liées aux fibres élastiques. De plus, identifier les facteurs impliqués dans les interactions épidermique­dermique des puces à l'aide des cytokines. RÉSULTATS: L'expression de l'EMILIN­1 dans les fibroblastes était augmentée en présence des kératinocytes, et son expression a diminué lorsque les keratinocytes ont été stressés. L'amphiréguline (AREG) et l'interleukine­1α (IL­1α) étaient identifiées comme les cytokines dérivées des kératinocytes qui influencent la production d'EMILIN­1, qui est sécrétée par les fibroblastes. L'expression d'EMILIN­1 était favorisée par l'AREG et diminuée par l'IL­1α via une augmentation de la cathepsine K (une enzyme catabolique). L'AREG et l'IL­1α étaient liés aux changements du niveau d'EMILIN­1 dans les fibroblastes. CONCLUSION: Les résultats montrent que la suppression de l'expression de l'IL­1α et la promotion de l'expression de l'AREG dans l'épiderme pourraient être une nouvelle approche qui prévient les rides et l'affaissement dus aux changements structurels des fibres élastiques.

Long Hanging Structure of Collagen VII Connects the Elastic Fibers and the Basement Membrane in Young Skin Tissue.

Aging leads to substantial structural changes in the skin. Elastic fibers maintain skin structure, but their degeneration and loss of function with age result in wrinkle formation and loss of skin elasticity. Oxytalan fiber, a type of elastic fiber, extends close to the dermal-epidermal junction (DEJ) from the back of the dermis. Oxytalan fibers are abundant in the papillary layer and contribute to skin elasticity and texture. However, to accurately understand the mechanisms of skin elasticity, the interaction between elastic fibers and DEJ should be elucidated. Here, we investigated elastic fibers and DEJ and their structural alterations with aging. Several basement membrane proteins [collagen (COL) IV, COLVII, and laminin 332], fibrous tropoelastin, and fibrillin-1 in excised human skin tissue were observed using three-dimensional imaging. Age-related alterations in COLVII, elastic fibers, and fibrillin-1 were evaluated. We found that COLVII forms long hanging structures and is co-localized with fibrous tropoelastin in young skin but not aged skin. Fibrillin-1-rich regions were observed at the tips of elastin fibers in young skin tissue, but rarely in aged skin. This co-localization of elastic fiber and COLVII may maintain skin structure, thereby preventing wrinkling and sagging. COLVII is a potential therapeutic target for skin wrinkling.

Trehangelins ameliorate inflammation-induced skin senescence by suppressing the epidermal YAP-CCN1 axis.

Trehangelins (THG) are newly identified trehalose compounds derived from broth cultures of an endophytic actinomycete, Polymorphospora rubra. THG are known to suppress Cellular Communication Network factor 1 (CCN1), which regulates collagen homeostasis in the dermis. Although the physical properties of THG suggest a high penetration of the stratum corneum, the effect of THG on the epidermis has not been reported. Here we describe a possible mechanism involved in skin aging focusing on the effect of THG on epidermal CCN1. This study shows that: (1) THG suppress epidermal CCN1 expression by inhibiting the translocation of Yes-Associated Protein (YAP) to nuclei. (2) Epidermal CCN1, localized at the basement membrane, regulates the balance between the growth and differentiation of keratinocytes. (3) Keratinocytes secrete more CCN1 than fibroblasts, which leads to disruption of the basement membrane and extracellular matrix components. (4) The secretion of CCN1 from keratinocytes is increased by ultraviolet B exposure, especially in aged keratinocytes, and deteriorates the elastic fiber structures in the underlying dermis. (5) Topical application of THG ameliorates the structure of the basement membrane in ex vivo human skin explants. Taken together, THG might be a promising treatment for aged skin by suppressing the aberrant YAP-CCN1 axis.

Elastin microfibril interface-located protein 1 and its catabolic enzyme, cathepsin K, regulate the age-related structure of elastic fibers in the skin.

INTRODUCTION: The elastic fiber structure becomes shorter, thicker, and curved with age. Nonetheless, the proteins and catabolic enzymes influencing the maintenance of and change in the three-dimensional (3D) structure of elastic fibers remain unknown. This study aimed to identify the proteins involved in the maintenance and degeneration of elastic fiber structures. METHODS: We performed a combined 3D structural analysis using tissue decolorization technology and mRNA abundance and comprehensive protein expression of tissue-derived cells. The relationship between the proteins was evaluated. RESULTS: Elastin microfibril interface-located protein 1 (EMILIN-1) and cathepsin K (CTSK) were implicated in structural changes in elastic fibers with aging. EMILIN-1 and CTSK levels were highly correlated and changed with age. CTSK was identified as the degrading enzyme of EMILIN-1. CTSK fragmented the otherwise linearly existing dermal elastic fiber structure, with more evident changes in oxytalan fibers. EMILIN-1 expression in fibroblasts was increased by co-culturing with keratinocytes. Furthermore, CTSK expression was increased by UV stress in keratinocytes, resulting in decreased EMILIN-1 expression. CONCLUSION: Using our new assessment strategy, we observed that EMILIN-1 and CTSK are highly linked to changes in the elastic fiber structure with aging. These results indicate that suppressing CTSK expression and increasing EMILIN-1 expression might be an effective approach to prevent elastic fiber morphological changes that lead to wrinkles and sagging. Furthermore, EMILIN-1 in the dermis increases due to interaction with the epidermis, which could provide a new target for the therapeutic care of elastic fibers (including preservation of oxytalan fibers) in epidermis-dermis interaction.

A Novel In Vitro Assay Using Human iPSC-Derived Sensory Neurons to Evaluate the Effects of External Chemicals on Neuronal Morphology: Possible Implications in the Prediction of Abnormal Skin Sensation.

Neuronal morphological changes in the epidermis are considered to be one of causes of abnormal skin sensations in dry skin-based skin diseases. The present study aimed to develop an in vitro model optimised for human skin to test the external factors that lead to its exacerbation. Human-induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) were used as a model of human sensory neurons. The effects of chemical substances on these neurons were evaluated by observing the elongation of nerve fibers, incidence of blebs (bead-like swellings), and the expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). The nerve fiber length increased upon exposure to two common cosmetic preservatives-methylparaben and phenoxyethanol-but not to benzo[a]pyrene, an air pollutant at the estimated concentrations in the epidermis. Furthermore, the incidence of blebs increased upon exposure to benzo[a]pyrene. However, there was a decrease in the expression of NMNAT2 in nerve fibers, suggesting degenerative changes. No such degeneration was found after methylparaben or phenoxyethanol at the estimated concentrations in the epidermis. These findings suggest that methylparaben and phenoxyethanol promote nerve elongation in hiPSC-SNs, whereas benzo[a]pyrene induces nerve degeneration. Such alterations may be at least partly involved in the onset and progression of sensitive skin.