Recent advances in characterizing biological mechanisms underlying UV-induced wrinkles: a pivotal role of fibrobrast-derived elastase

In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Cumulative irradiation with ultraviolet (UV) B at suberythemal doses significantly reduces the elastic properties of the skin, resulting in the formation of wrinkles. In in vitro studies, we identified a paracrine pathway between keratinocytes and fibroblasts, which leads to wrinkle formation via the up-regulation of fibroblast elastases that degrade elastic fibers. UVB irradiation stimulates the activity of fibroblast elastases in animal skin. Scanning electron microscopy revealed that cumulative UVB irradiation elicits a marked alteration in the three-dimensional structure of elastic fibers, which is closely associated with the subsequent reduction in the elastic properties of the skin, resulting in wrinkle formation. Studies using anti-wrinkle treatments suggest a close relationship between the recovery of wrinkles and an improvement in the linearity of elastic fibers. Those studies also suggest a close correlation between the recovery in the linearity of elastic fibers and the improvement in skin elasticity. In a study using ovariectomized animals, we characterized the important role of elastase in their high vulnerability to UV-induced wrinkle formation. A synthetic inhibitor specific for fibroblast elastases significantly prevents wrinkle formation without reducing the elastic properties of the skin, accompanied by minor damage in elastic fibers. Finally, we identified an effective extract of Zingiber officinale (L.) Rose from a screen of many herb extracts, which has a safe and potent inhibitory activity against fibroblast elastases. Animal studies using the L. Rose extract revealed that it has significant preventive effects against UVB-induced wrinkle formation, which occur in concert with beneficial effects on skin elasticity. A 1-year clinical study on human facial skin to determine the efficacy of the L. Rose extract demonstrated that it inhibits the UV-induced decrease in skin elasticity and prevents or improves wrinkle formation in skin around the corner of the eye without changing the water content of the stratum corneum. Our long-term studies support our hypothesis for a mechanism of wrinkle formation in which cytokine expression is activated by UV irradiation and triggers dermal fibroblasts to increase the expression of elastase. That increase in elastase results in the deterioration of the three-dimensional architecture of elastic fibers, reducing skin elasticity and finally leading to the formation of wrinkles.     

Epidermal changes caused by chronic low-dose UV irradiation induce wrinkle formation in hairless mouse

To investigate the effects of chronic low-dose UV irradiation on the skin, hairless mice were irradiated with a 1/3 minimal erythemal dose (MED) of UV. We examined the relationship between visible changes and skin damage in the dermis and epidermis. Hairless mice were irradiated with UVB (20 mJ/cm2) and UVA (14 J/cm2) three times a week for 10 weeks, followed by a 24-week non-irradiation period. Visible fine wrinkling was present after 4 weeks of irradiation, and the wrinkling progressively worsened throughout the period of irradiation. The wrinkles remained after irradiation was discontinued. In dermal components, no significant histological changes in the collagen fibers and elastic fibers were found, and the amount of hydroxyproline was also not changed. Thus, in the epidermis, there was a significant increase in the number of stratum corneum layers and the terminal-differentiation marker, filaggrin, positive cells. The intensity of staining for the differentiation marker, keratin 1, was reduced. These changes were accompanied by wrinkle formation, and remained after discontinuance of irradiation. These findings suggested that chronic low-dose UV irradiation induces structural and quantitative changes in the epidermis as a result of keratinization impairment, and that this damage in the epidermis is an important causative factor in wrinkle formation.     

Unusual wrinkle formation after temporary skin fixation followed by UVB irradiation in hairless mouse skin

Abstract Generally, many wrinkles form on the human face, and temporary wrinkles eventually become permanent. We evaluated the effects of temporary skin fixation on wrinkle formation after UVB irradiation using the back skin of hairless mice. In the group treated with UVB irradiation immediately after production using cyanoacrylate resin of an artificial groove parallel to the midline, wrinkles formed parallel to the midline, an uncommon direction for wrinkle formation in this mouse model. These wrinkles did not disappear even when the skin was stretched. No such changes were observed in the group in which only the temporary groove alone was produced without UVB irradiation. In 3-D surface parameter analysis, all roughness parameters in the group treated with UVB irradiation immediately after production of an artificial groove were significantly increased relative to the age-matched control group. In contrast, no differences were observed between the group in which only the temporary groove alone was produced without UVB irradiation and age-matched controls. The results of this study suggest that both a temporary groove in the skin and UVB irradiation are necessary for wrinkle formation in the back skin of hairless mice.     

Carbon dioxide laser treatment promotes repair of the three-dimensional network of elastic fibres in rat skin

BACKGROUND: We have previously reported that ultraviolet (UV) B irradiation induces a loss of linearity in the three-dimensional structure of dermal elastic fibres, which results in the reduction of elastic properties of the skin and leads to wrinkle formation. We further reported that repair of wrinkles by all-trans retinoic acid is accompanied by recovery of the linearity of elastic fibres. Carbon dioxide (CO2) lasers are widely used for treating wrinkles in cosmetic surgery. OBJECTIVES: To perform CO2 laser treatment of wrinkles induced in rat skin by UVB irradiation and to evaluate changes in the three-dimensional structure of dermal elastic fibres during wrinkle repair. METHODS: Wrinkles were induced in the hind limb skin of Sprague-Dawley rats by UVB irradiation (130 mJ cm-2 three times weekly for 6 weeks), followed by CO2 laser treatment (11.3 J cm-2). The surface appearance of the skin was evaluated by replica observation 6 and 10 weeks after CO2 laser treatment followed by measurement of mechanical properties using a Cutometer. Subsequently, perfusion fixation and digestion with formic acid were performed and elastic fibres were observed by scanning electron microscopy (SEM). Image analysis of SEM micrographs was carried out to evaluate the linearity in the three-dimensional structure of elastic fibres. RESULTS: Six weeks after CO2 laser treatment, all parameters of skin mechanical properties in the UVB-irradiated group recovered to levels of the control non-irradiated group, accompanied by repair of wrinkles and a significant increase in linearity of the three-dimensional structure of elastic fibres. CONCLUSIONS: These findings indicate that CO2 laser treatment has a therapeutic potential to repair wrinkles to non-irradiated levels through recovery of the three-dimensional structure of elastic fibres.     

Biophysical and morphological changes in the stratum corneum lipids induced by UVB irradiation

BACKGROUND: UV irradiation induces a variety of responses in the epidermis, including sunburn cell formation, epidermal hyperplasia, and epidermal permeability barrier disruption. OBJECTIVE: The aim of present study was to assess the effects of UVB irradiation in the intercellular lipids in murine stratum corneum. METHODS: Adult hairless mice were exposed to a single UVB dose (0.15 J/cm(2)), the Fourier transform infrared (FT-IR) spectroscopic study was performed to investigate the effect on the biophysical changes in the stratum corneum lipids, barrier function was monitored by transepidermal water loss (TEWL) measurement, and the morphological alterations of stratum corneum was examined by electron microscopy using ruthenium tetroxide postfixation. RESULTS: The FT-IR spectroscopic study revealed that there was the shift to higher wavenumbers of the symmetric and asymmetric stretching peaks near 2850 and 2920 cm(-1) respectively at days 3-4 after a single UVB irradiation, reflecting to the increase in motional freedom of lipids hydrocarbon chains, call as disordering of lipids. Moreover, A single UVB irradiation also caused a significant increase in TEWL, the increase in TEWL began after 2 days and peaked at day 4. Electron microscopic observations revealed that marked morphological abnormalities in the intercellular domains, including abnormal profile of lamellar granules and its contents at the interface between stratum corneum and stratum granulosum and the persistence of the nuclei in the stratum corneum. Moreover, the separated fragmentary lipid lamellae, excessive numbers of lamellae in stacks, both the elongated and enlarged lacuna as well as the extracellular whorls were present within the widen space of the stratum corneum. CONCLUSION: The both of biophysical and morphological changes of the stratum corneum lipids may reflect to the mechanisms of perturbation of the epidermal permeability barrier induced by UVB irradiation.     

Ovariectomy is sufficient to accelerate spontaneous skin ageing and to stimulate ultraviolet irradiation-induced photoageing of murine skin

Background: Wrinkling and sagging of the skin during photoageing is physiologically associated with diminished elasticity, which can be attributed to increased fibroblast-derived elastase activity. This degrades the dermal elastic fibres needed to maintain the three-dimensional structure of the skin. We previously reported that ovariectomy accelerates ultraviolet (UV)B-induced wrinkle formation in rat hind limb skin by altering the three-dimensional structure of elastic fibres. OBJECTIVES: In this study, we used hairless mice to assess the effects of ovariectomy with or without chronic UVA or UVB radiation on sagging and wrinkling of skin, on the elasticity of skin, as well as on matrix metalloproteinase activities in the skin. METHODS: Ovariectomies or sham operations were performed on 6-week-old female ICR/HR hairless mice. RESULTS: Even in the ovariectomy group without UV irradiation, the skin elasticity was significantly decreased during the 3-13 weeks after ovariectomy, which was accompanied by a significant increase in elastase activity in the skin. After UVA or UVB irradiation, skin elasticity was significantly decreased to a greater extent in the ovariectomy group than in the sham operation group, and this was accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV in the skin. Consistent with the decreased skin elasticity, UVA irradiation for 12 weeks elicited more marked sagging in the ovariectomy group than in the sham operation group. UVB irradiation for 12 weeks also induced more marked wrinkle formation in the ovariectomy group than in the sham operation group. CONCLUSIONS: These results suggest that ovariectomy alone is sufficient to accelerate skin ageing and to increase UV sensitivity, which results in the further deterioration of the skin and photoageing, and may account for the accelerated skin ageing seen in postmenopausal women.     

An accumulation of glucosylceramide in the stratum corneum due to attenuated activity of beta-glucocerebrosidase is associated with the early phase of UVB-induced alteration in cutaneous barrier function

Epidermal glucosylceramide (GlcCer) metabolism is essential to the maintenance of skin homeostasis. Although exposure of the skin to ultraviolet (UV) radiation elicits dramatic physiological and biological changes in the epidermis attributable to barrier perturbation, wrinkle formation and inflammation, little is known about UV-induced changes in GlcCer metabolism. In this study, we have assessed β-glucocerebrosidase (GlcCer’ase) activity in murine epidermis before and after a single UVB irradiation and have compared it with GlcCer and ceramide (Cer) levels. GlcCer’ase enzymatic activity was significantly suppressed in a dose-dependent manner one day after UVB (70 mJ/cm²) irradiation despite a significant increase in GlcCer’ase mRNA. The marked decrease in enzyme activity was followed by an accumulation of GlcCer in the stratum corneum, which peaked at day 2. This decreased level of GlcCer’ase activity returned to 80% of the control level by day 3 followed by a return of GlcCer level to the control level by day 4. In the whole epidermis, significant increases in Cer and GlcCer levels occurred on day 3 and on day 2, respectively. These results suggest that UVB irradiation dramatically affects the metabolism of GlcCer to Cer in the epidermis (including the stratum corneum) and that this may be closely associated with the early and minor phase of UVB-induced alteration in cutaneous barrier function.     

Relationship between covalently bound ceramides and transepidermal water loss (TEWL)

The stratum corneum, which is the outermost layer of the skin, functions as an important barrier to maintain biological homeostasis. The multilamellar structures formed by intercellular lipids present in the stratum corneum are considered to play an important role in barrier function. Most intercellular lipids are unbound and can be extracted by organic solvents, but some intercellular lipids are covalently bound to cornified envelope proteins. Decreases in unbound lipid levels reduce the barrier function of the stratum corneum, but the relationship between bound lipid and the barrier function of the stratum corneum is not well understood. In this study, we examined the relationship between the amount of covalently bound ceramide, the main bound lipid, and the barrier function of the stratum corneum. A single dose of UVB irradiation (2 x MED), or continuous UVB irradiation (0.5 x MED/day for 14 days) to the back, or feeding with an essential fatty acid-deficient (EFAD) diet for 8 weeks caused a significant elevation of TEWL and a significant reduction in covalently bound ceramides in hairless rats. Transmission electron microscopy revealed that the intercellular multilamellar structures in the stratum corneum of treated rats were incomplete (folding, defects, unclear images) compared to the structures seen in the stratum corneum of non-UVB-irradiated and non-EFAD rats. These results suggest that the amount of covalently bound ceramides is highly correlated with the barrier function of the skin, and that covalently bound ceramides play an important role in the formation of lamellar structures, and are involved in the maintenance of the barrier function of the skin.     

Inhibition of ultraviolet-B-induced wrinkle formation by an elastase-inhibiting herbal extract: implication for the mechanism underlying elastase-associated wrinkles

BACKGROUND: Previously, we have demonstrated that fibroblast-derived elastase plays an essential role in the increased three-dimensional tortuosity of elastic fibers, contributing to the loss of skin elasticity in UV-B-exposed skin. This decrease in skin elasticity is closely associated with the formation of wrinkles induced by UV exposure. OBJECTIVE: To further clarify the role of elastase in the formation of wrinkles induced by UV exposure, we assessed the effects of an extract of Zingiber officinale (L.) Rose (which inhibits fibroblast-derived elastase) on the wrinkle formation induced by chronic UV-B irradiation. RESULTS: Topical application of an extract of Zingiber officinale (L.) Rose to rat or hairless mouse skin significantly inhibited the wrinkle formation induced by chronic UV-B irradiation at a suberythemal dose, which was accompanied by a significant prevention of the decrease in skin elasticity in both types of animal skin. In the rat hind limb skin, consistent with the inhibition of reduced skin elasticity, wrinkle prevention occurred concomitantly with a significant decrease in the curling and three-dimensional tortuosity of dermal elastic fibers. CONCLUSION: Our results indicate that herbal extracts with an ability to inhibit fibroblast-derived elastase may prove to be effective as anti-wrinkling agents, confirming the important role of elastase in UV-B-induced wrinkle formation.     

Decreased levels of covalently bound ceramide are associated with ultraviolet B-induced perturbation of the skin barrier

Although ultraviolet B (UVB) irradiation perturbs the skin barrier, little is known about the mechanism(s) with respect to the metabolism of ceramide (Cer). We examined changes in intercellular lipids in murine stratum corneum following UVB irradiation. A single UVB (75 mJ per cm(2)) irradiation caused a significant increase in transepidermal water loss, which plateaued at day 4. In parallel, covalently bound Cer was significantly decreased with the greatest decrease at days 3-4. In contrast, the levels of other free, non-bound lipids (including Cer or acylceramides) were significantly increased for Cer, or remained unchanged at day 4 compared with non-irradiated controls. RT-PCR analysis demonstrated a significant decrease in mRNA encoding transglutaminase-1 (TGase1). The peak occurred 2-4 d after a single UVB irradiation, a time when covalently bound Cer was significantly downregulated in concert with the disruption of the skin barrier. Furthermore, UVB-induced epidermal hyperplasia occurred to the greatest extent between 2 and 4 d following UVB irradiation. These results suggest that decreases in covalently bound Cer in the stratum corneum are mediated via the downregulation of TGase-1 as well as by the rapid induction of epidermal hyperplasia, which is attributable to the perturbation of the skin barrier induced by UVB irradiation.     

Effect of skin pH for wrinkle formation on Asian: Korean,Vietnamese and Singaporean

Background Skin pH may be influenced by various factors, such as hydration of stratum corneum, rate of sebum excretion rate, transepidermal water loss (TEWL) and sweating in relation to skin ageing. Objective The aim of this study was to evaluate the correlation between skin pH and wrinkle formation that is directly related to ageing. In addition, we investigated the factors related to skin ageing by comparing the association between skin pH and other skin properties. Methods Three hundred volunteers were selected from three countries: Korea, Vietnam and Singapore. Hydration on the stratum corneum, the rate of sebum excretion rate, melanin index, TEWL and skin temperature on the cheek were measured in a controlled room, and wrinkle length and depth using replicas were compared with skin pH variation. Results The mean and standard deviation of skin surface pH among the three countries were 5.510 ± 0.625. The greatest gap of skin pH that revealed significant differences for skin properties was represented between the Koreans and the Vietnamese. For all three countries, skin hydration, melanin contents, wrinkle length, wrinkle depth and skin temperature were significantly correlated with skin pH. Factors related to skin moisturizing, such as skin hydration, sebum excretion rate and skin temperature, were negatively correlated with skin pH. Wrinkle length and depth decreased as skin pH became more acidic. Conclusions Skin properties displayed various values depending on skin pH. In particular, wrinkle formation significantly decreased as skin pH becomes more acidic. We conclude that skin pH is determined by skin properties, such as skin hydration, sebum excretion rate, melanin concentration, TEWL and skin temperature that affects wrinkle formation.     

Ultraviolet B-induced alterations of the skin barrier and epidermal calcium gradient

Ultraviolet irradiation induces a variety of cutaneous changes, including epidermal permeability barrier disruption. In the present study, we assessed the effects of ultraviolet B (UVB) irradiation in epidermal barrier function and calcium distribution in murine epidermis. Adult hairless mice were exposed to a single dose of UVB (0.15 J/cm(2)). Barrier function was evaluated by transepidermal water loss (TEWL), lanthanum perfusion. The morphological alterations were examined by histology, immunohistochemistry and electron microscopy using ruthenium tetroxide (RuO(4)) postfixation. For evaluation of the effect on epidermal calcium distribution, the ion-capture cytochemistry was employed. UVB irradiation caused a significant increase in TEWL, which peaked at day 4. In parallel, the increased number of sunburn cells and the changes in epidermal hyperplasia and proliferation were observed. Electron microscopic observation demonstrated that the water-soluble lanthanum tracer was present in the extracellular stratum corneum domains, and the increased intercellular permeability was correlated with defective organization of the extracellular lipid lamellar bilayers of the stratum corneum. Moreover, UVB irradiation also caused an appearance of calcium precipitates in the stratum corneum and transitional cell layers as well as the increased cytosolic calcium in the lower epidermis, reflecting the alterations of the epidermal calcium gradient. These results suggest that the changes of the epidermal calcium distribution pattern may correlate with the perturbation of the epidermal barrier induced by UVB irradiation.     

Characteristics of skin wrinkling and dermal changes induced by repeated application of squalene monohydroperoxide to hairless mouse skin

We have studied the effect of squalene monohydroperoxides (Sq-OOH), initial products of UV-peroxidated squalene, on the skin of hairless mice. Repeated topical application of 10 mM Sq-OOH to hairless mice for 15 weeks induced definite skin wrinkling. When image analysis was used to compare wrinkle formation induced by ultraviolet B (UVB) irradiation and Sq-OOH treatment, the degree of wrinkling in exposed skin was seen to be similar. However, the characteristics of wrinkles induced by either method differed markedly with regard to direction and distribution. Biochemical analysis revealed a significant decrease in collagen content per unit area and mass in Sq-OOH-treated skin, whereas no changes per unit area and decrease in collagen per unit mass were observed in UVB-irradiated skin. As for glycosaminoglycan (GAG) content per unit area, significant increases were observed in both Sq-OOH-treated skin and UVB-irradiated skin. These changes were not induced by organic hydroperoxides such as TERT-butylhydroperoxide or cumene hydroperoxide treatment. Histological observation revealed epidermal hyperplasia and dermal alterations such as collagen degradation and GAG increases in Sq-OOH-treated skin. Histological changes induced by Sq-OOH were not as pronounced as those induced by UVB irradiation. These results clearly suggest that the wrinkling and changes in dermal collagen content induced by Sq-OOH are qualitatively different to those induced by UVB exposure. This may provide a useful model for the study of skin aging, particularly with regard to collagen content.     

Effects of ultraviolet A and B on the skin barrier: a functional, electron microscopic and lipid biochemical study.

To investigate the effects of ultraviolet A (UVA) and B (UVB) on the skin barrier, functional, electron microscopic and lipid biochemical studies were performed on normal and UV-irradiated skin of volunteers. Skin reactivity against primary irritants was evaluated using the alkali resistance test, the dimethylsulfoxide test and the sodium lauryl sulfate test. In all 3 irritation models, UVA- and UVB-irradiated areas were more resistant to damage than normal skin, indicating improvement of the barrier function after UV irradiation. In a second series of experiments, biopsies were taken and processed for electron microscopic evaluation of the stratum corneum. UVB significantly increased the horny cell layers; UVA did not alter the thickness of the stratum corneum. Finally, stratum corneum lipids were extracted in vivo and quantified after high-performance thin-layer chromatography. UVB and, to some extent, UVA exposure increased the amount of all stratum corneum lipids. This was also observed in all major ceramide subfractions.     

The effect of ultraviolet radiation on the water-reservoir functions of the stratum corneum.

The stratum corneum plays an important role in keeping the skin surface supple and flexible. After exposure to sunlight, the skin may become dry and scaly. In the present study, the water content, hygroscopicity and water-holding capacity of the stratum corneum were examined after ultraviolet B (UVB) exposure to the guinea pig skin. Manually depilated back skin was exposed once to 1, 2 and 3 times the minimal erythema dose of UVB, and a time course study was performed. Our study demonstrated the following: The water content, water-holding capacity and hygroscopicity decreased after UVB irradiation. They decreased roughly dependent on UVB dose. The decreased water content and water-holding capacity were noted on day 1 and persisted until day 10 to 14. In contrast, the decrease in hygroscopicity became apparent 3 days after exposure and returned to the preirradiated state on day 7. The impaired functional parameters were partially prevented by topical application of a sunscreen. These results indicate that a single exposure to UVB can damage the function of the stratum corneum.     

Mechanics of wrinkle formation: micromechanical analysis of skin deformation during wrinkle formation in ultraviolet‐irradiated mice

Background/purpose: The mechanical aspects of wrinkle formation were studied in the dorsal skin of hairless mice. Methods: Wrinkles were induced by irradiating with ultraviolet (UV) B for 10 weeks, while observing skin deformation during wrinkle formation. Changes in skin dimensions were also observed during the specimen excision process. Wrinkle depth and interval were measured before and after removal of the cutaneous muscle layer. Local deformation of wrinkled skin during uniaxial stretch was also measured. Changes in curvature of skin specimens upon muscle layer removal were then observed to determine the force balance in skin layers. Results: The skin showed spontaneous contraction in response to UV irradiation. Wrinkled skin showed a marked decrease in the wrinkle depth and a slight increase in wrinkle interval following muscle layer removal, a peculiar mechanical response that cannot be explained by homogeneous deformation of the skin. This response was due to compressive deformations of dermal tissue caused by the muscle layer and concentrated at valleys of the wrinkles. Curvature measurements indicated that the muscle layer compressed the dermal tissue predominantly in the craniocaudal direction. Morphological observations showed that the wrinkles coincided with rows of pores and sulci cutis, where the structural stiffness of the horny layer was relatively low. The horny layer showed significant thickening. Conclusion: Taken together, we propose the following hypothetical mechanisms of wrinkle formation during UV irradiation: spontaneous contraction of the dermis while maintaining or increasing the epidermal area induces buckling of the epidermis into the dermis at mechanically weak lines, namely, the rows of pores and sulci cutis, and buckling may be amplified by the axial compression of the dermis by the muscle layer.     

Skin rejuvenating effects of chemical peeling: a study in photoaged hairless mice

Background Chemical peeling is a dermatologic treatment for skin aging. However, the mechanism by which the chemical peel achieves its results is not clear. We investigated the effects of chemical peeling and the mechanism of wrinkle reduction in photoaged hairless mice skin. Methods After inducing photoaged skin in hairless mice by repetitive ultraviolet‐B irradiation applied over 14 weeks, we applied trichloroacetic acid (TCA) 30%, TCA 50%, and phenol on areas of the same size on the backs of the mice. Punch biopsies were obtained 7, 14, 28, and 60 days after the procedure for histologic and immunohistochemical analyses. Results Histologic examination showed an increase in dermal thickness, collagen fibers, and elastic fibers in the dermis of intervention groups compared with control groups. These increases were maintained significantly for 60 days. Conclusions This study demonstrates that chemical peeling reduces wrinkles and regenerates skin by increasing dermal thickness and the amount of collagen and elastic fibers in photoaged skin.     

Squamometry in acute photodamage

Background: Ultraviolet Irradiation has been shown to elicit alterations in corneocyte adhesion.
Purpose: To evaluate the early events in the changes of physical properties of the stratum corneum following a single ultraviolet B (UVB) irradiation.
Method: Squamometry (Chroma C* of D-Squames) was used in 40 volunteers to assess the variations in stratum corneum cohesion during 3 consecutive days following 1.5 MED UVB irradiation on the forearms.
Results: Subjects with normal or moderately dry skin showed a significant increase in squamometry values during the 24 or 48 h following irradiation. Subjects with severe xerosis showed a progressive decrease in that value over time.
Conclusions: UV-Squamometry is a convenient, rapid and sensitive method for evaluating the direct effect of UVB radiation on the stratum corneum.     

Loss of elastic fibers causes skin wrinkles in sun-damaged human skin

BACKGROUND: Although wrinkling is the most obvious sign of aged skin, the detailed pathomechanism of wrinkle development has not been elucidated. OBJECTIVES: In this study, we investigated the role of elastic fibers in the formation of skin wrinkles. METHODS: Loss of elastic fibers was measured quantitatively in the facial skins of subjects representing seven decades, and then compared with wrinkle severities. We also investigated whether topical retinoic acid treatment to photoaged human skin can restore destroyed elastic fiber, and the correlation between wrinkle improvement with increase in elastic fibers in RA-treated facial skin. RESULTS: We found a significant correlation between decreases in the length, width, number and total area of oxytalan fibers and wrinkle severity. Furthermore, we found that topical application of retinoic acid (0.025%) to chronically photodamaged skin regenerated and restored elastic fibers, and that there was a significant positive correlation between the amount of newly regenerated elastic fiber and the wrinkle improvement caused by retinoic acid. CONCLUSIONS: Our results provide an objective insight into the role of elastic fibers in skin wrinkle formation by providing a quantitative correlation between changes in oxytalan fibers and the severity of skin wrinkling.