Skin Aging Abstracts 1

©

The role of biologically active peptides in tissue repair using umbilical cord mesenchymal stem cells

         (Cabrera, Carriquiry et al. 2012) Download

The role of bioactive compounds in wound repair is critical. The preliminary work described herein includes the study of the effects of second degree burns in a Rex rabbit model and the action of human umbilical cord cells on the regulation and secretion of bioactive compounds. When applied on blood scaffolds as heterograft matrices, fibroblasts proliferate from these primary cultures and release biologically active peptides under tight control. Our work in progress indicates that mesenchymal stem cell (MSC)-mediated therapy provides better quality and more efficient burn reepithelialization of injured tissues by controlling the release of these peptides. Improvement of wound aesthetics is achieved in less time than without MSC-mediated therapy. Well-organized epidermal regeneration and overall better quality of reepithelialization, with no rejection, can be demonstrated consistently with periodic biopsies. Our studies indicate that MSCs have the capacity to produce, regulate, and deliver biologically active peptides that result in superior regeneration, compared with conventional treatments.

Cutaneous concentration of lycopene correlates significantly with the roughness of the skin

         (Darvin, Patzelt et al. 2008) Download

Antioxidant substances in the skin are expected to slow down photo ageing. We therefore developed the hypothesis that high levels of antioxidant substances may be correlated to lower levels of skin roughness. By utilizing modern optical non-invasive in vivo methods, the structures of the furrows and wrinkles as well as the concentration of lycopene were analyzed quantitatively on the forehead skin of 20 volunteers aged between 40 and 50 years. In a first step, the age of the volunteers was correlated to their skin roughness. Here, no significant correlation was found. In a second step, a significant correlation was obtained between the skin roughness and the lycopene concentration (R=0.843). These findings indicate that higher levels of antioxidants in the skin effectively lead to lower levels of skin roughness, and therefore support our hypothesis.

Oral administration of French maritime pine bark extract (Flavangenol((R))) improves clinical symptoms in photoaged facial skin

         (Furumura, Sato et al. 2012) Download

BACKGROUND: French maritime pine bark extract (PBE) has gained popularity as a dietary supplement in the treatment of various diseases due to its polyphenol-rich ingredients. Oligometric proanthocyanidins (OPCs), a class of bioflavonoid complexes, are enriched in French maritime PBE and have antioxidant and anti-inflammatory activity. Previous studies have suggested that French maritime PBE helps reduce ultraviolet radiation damage to the skin and may protect human facial skin from symptoms of photoaging. To evaluate the clinical efficacy of French maritime PBE in the improvement of photodamaged facial skin, we conducted a randomized trial of oral supplementation with PBE. METHODS: One hundred and twelve women with mild to moderate photoaging of the skin were randomized to either a 12-week open trial regimen of 100 mg PBE supplementation once daily or to a parallel-group trial regimen of 40 mg PBE supplementation once daily. RESULTS: A significant decrease in clinical grading of skin photoaging scores was observed in both time courses of 100 mg daily and 40 mg daily PBE supplementation regimens. A significant reduction in the pigmentation of age spots was also demonstrated utilizing skin color measurements. CONCLUSION: Clinically significant improvement in photodamaged skin could be achieved with PBE. Our findings confirm the efficacy and safety of PBE.

Protection from photodamage by topical application of caffeine after ultraviolet irradiation

         (Koo, Hirakawa et al. 2007) Download

BACKGROUND: Characterization of mechanisms that can reverse residual damage from prior skin exposure to ultraviolet (UV) would be of considerable biological and therapeutic interest. Topical caffeine application to mouse skin that had previously been treated with UV has been shown to inhibit the subsequent development of squamous cell carcinomas. OBJECTIVES: We used an established mouse photodamage model to investigate other possible effects of topical caffeine application after UV. METHODS: SKH-1 hairless mice were treated with ultraviolet B (UVB) followed immediately by topical application of caffeine or vehicle three times weekly for 11 weeks. RESULTS: Caffeine applied topically after UV treatment resulted in a significant decrease in UV-induced skin roughness/transverse rhytides as assessed by treatment-blinded examiners. Histologically, topical caffeine application after a single dose of UVB more than doubled the number of apoptotic keratinocytes as evaluated by sunburn cell formation, caspase 3 cleavage and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) staining. A trend towards decreased solar elastosis was noted in the caffeine-treated group although this was not statistically significant. Other histological parameters including epidermal hyperplasia, solar elastosis and angiogenesis were increased in mice treated with UV but topical application of caffeine did not alter these particular UV effects. CONCLUSIONS: These findings support the concept that topical application of caffeine to mouse skin after UV irradiation promotes the deletion of DNA-damaged keratinocytes and may partially diminish photodamage as well as photocarcinogenesis.

Modulation of collagen synthesis and its gene expression in human skin fibroblasts by tocotrienol-rich fraction

         (Makpol, Azura Jam et al. 2011) Download

INTRODUCTION: Skin aging may occur as a result of increased free radicals in the body. Vitamin E, the major chain-breaking antioxidant, prevents propagation of oxidative stress, especially in biological membranes. In this study, the molecular mechanism of tocotrienol-rich fraction (TRF) in preventing oxidative stress-induced skin aging was evaluated by determining the rate of total collagen synthesis and its gene expression in human skin fibroblasts. MATERIAL AND METHODS: Primary culture of human skin fibroblasts was derived from circumcision foreskin of 9 to 12 year-old boys. Fibroblast cells were divided into 5 different treatment groups: untreated control, hydrogen peroxide (H(2)O(2))-induced oxidative stress (20 microM H(2)O(2) exposure for 2 weeks), TRF treatment, and pre- and post-treatment of TRF to H(2)O(2)-induced oxidative stress. RESULTS: Our results showed that H(2)O(2)-induced oxidative stress decreased the rate of total collagen synthesis and down-regulated COL I and COL III in skin fibroblasts. Pre-treatment of TRF protected against H(2)O(2)-induced oxidative stress as shown by increase in total collagen synthesis and up-regulation of COL I and COL III (p<0.05) genes. However, similar protective effects against H(2)O(2)-induced oxidative stress were not observed in the post-treated fibroblasts. CONCLUSIONS: Tocotrienol-rich fraction protects against H(2)O(2)-induced oxidative stress in human skin fibroblast culture by modulating the expression of COL I and COL III genes with concomitant increase in the rate of total collagen synthesis. These findings may indicate TRF protection against oxidative stress-induced skin aging.

A novel anti-ageing mechanism for retinol: induction of dermal elastin synthesis and elastin fibre formation

         (Rossetti, Kielmanowicz et al. 2011) Download

Dermal elastic fibres are extracellular matrix protein complexes produced by fibroblasts and involved in skin elasticity. Elastin fibres decrease with age as a result of reduced synthesis and increased degradation, resulting in skin sagging and reduced skin elasticity. In this study, we show that retinol (ROL), known to enhance dermal collagen production, is also enhancing elastin fibre formation. ROL induced elastin gene expression and elastin fibre formation in cultured human dermal fibroblasts. Topical treatment of cultured human skin explants with a low dose (0.04%) of ROL increased mRNA and protein levels of tropoelastin and of fibrillin-1, an elastin accessory protein, as documented by QPCR and immunohistochemistry staining. Luna staining confirmed the increased elastin fibre network in the ROL-treated skin explants, as compared with untreated controls. These data demonstrate that ROL exerts its anti-ageing benefits not only via enhanced epidermal proliferation and increased collagen production, but also through an increase in elastin production and assembly.

Immediate and Long-term Clinical Benefits of a Topical Treatment for Facial Lines and Wrinkles

         (Trookman, Rizer et al. 2009) Download

Objective: To evaluate the efficacy and tolerance of a novel line treatment for periocular and perioral wrinkles. The line treatment was formulated with multiple growth factors, antioxidants, and a collagen-building peptide-ingredients that have been shown to increase collagen levels and provide long-term aesthetic benefits. To help provide immediate smoothing effects, hyaluronic acid filling spheres and a muscle contraction-inhibiting peptide were also included in the formulation. Design: Three-month, single-center, open-label, clinical study with clinical assessments at Baseline, Minutes (within 15 minutes of initial application), Month 1, and Month 3. Treatment: Subjects treated periocular and perioral wrinkles twice daily for three months with the line treatment. Participants: Thirty-seven females, 33 to 45 years of age, with mild-to-moderate, fine and coarse periocular and perioral wrinkles, were enrolled in the study. Measurements: Investigator assessments of fine and coarse periocular and perioral wrinkles, digital photography, and tolerance assessments were conducted at all visits. Subject self-assessment questionnaires were conducted within 15 minutes of initial application and at Month 3. Results: Investigator assessments of both periocular and perioral wrinkles showed statistically significant improvements over Baseline within minutes of initial application; these positive findings continued to improve through Months 1 and 3 (all P</=0.0003). No treatment-related adverse events were reported. Conclusions: The results from this study demonstrate that this uniquely formulated line treatment was well tolerated and provided both immediate and long-term improvements in the appearance of fine and coarse wrinkles.

Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin

         (Varani, Warner et al. 2000) Download

Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.

Effect of green Coffea arabica L. seed oil on extracellular matrix components and water-channel expression in in vitro and ex vivo human skin models

         (Velazquez Pereda Mdel, Dieamant Gde et al. 2009) Download

BACKGROUND: Green Coffea arabica L. seed oil is being widely used in cosmetic formulations, although its effects on human skin cells are not clear and most observations are unpublished. AIMS: In this study, we evaluated the in vitro effects of green coffee (C. arabica L.) oil (GCO) on the synthesis of collagen, elastin, and glycosaminoglycans (GAG) and in the release of transforming growth factor-beta1 (TGF-beta1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by human skin fibroblasts. We also investigated the ability of GCO to increase aquaglycerolporins-3 (AQP-3) mRNA expression in cultured keratinocytes and human skin explants. METHODS: Human fibroblasts were incubated for 48 h with several GCO concentrations (3.12, 6.25, 12.5, 25.0 and 50.0 mg/mL). The levels of growth factors and extracellular matrix compounds in the culture supernatant were measured using commercial kits. To evaluate AQP-3 relative expression, using real-time reverse transcription polymerase chain reaction, keratinocytes were incubated for 3-6 h with the GCO optimal concentration of 25.0 mg/mL. Histological sections of human skin were also incubated with GCO (25.0 mg/mL) and immunostained by antiserum against AQP-3. RESULTS: Our results demonstrated that incubation with GCO produces a dose-dependent stimulation in the synthesis of collagen, elastin, and GAG, in addition to increasing the release of the growth factors TGF-beta1 and GM-CSF. GCO also induced the expression of AQP-3 mRNA, which reached levels up to 6.5-fold higher than those of the control cultures. CONCLUSION: The findings presented herein suggest that GCO might improve physiological balance in the skin, thus allowing the formation of new connective tissue, and preventing epidermis dryness by increasing AQP-3 levels. Taking into account the limitations of in vitro studies, it is encouraging in this context to consider CGO as an adjuvant to be used in dermocosmetic formulations. Clinical studies are in progress in our laboratory aiming to further investigate the protective effects of CGO in the skin.

Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts

         (Yoon, Kim et al. 2012) Download

The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the beta1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles.


References

Cabrera, C., G. Carriquiry, et al. (2012). "The role of biologically active peptides in tissue repair using umbilical cord mesenchymal stem cells." Ann N Y Acad Sci 1270: 93-7. [PMID: 23050823]

Darvin, M., A. Patzelt, et al. (2008). "Cutaneous concentration of lycopene correlates significantly with the roughness of the skin." Eur J Pharm Biopharm 69(3): 943-7. [PMID: 18411044]

Furumura, M., N. Sato, et al. (2012). "Oral administration of French maritime pine bark extract (Flavangenol((R))) improves clinical symptoms in photoaged facial skin." Clin Interv Aging 7: 275-86. [PMID: 22956863]

Koo, S. W., S. Hirakawa, et al. (2007). "Protection from photodamage by topical application of caffeine after ultraviolet irradiation." Br J Dermatol 156(5): 957-64. [PMID: 17388926]

Makpol, S., F. Azura Jam, et al. (2011). "Modulation of collagen synthesis and its gene expression in human skin fibroblasts by tocotrienol-rich fraction." Arch Med Sci 7(5): 889-95. [PMID: 22291837]

Rossetti, D., M. G. Kielmanowicz, et al. (2011). "A novel anti-ageing mechanism for retinol: induction of dermal elastin synthesis and elastin fibre formation." Int J Cosmet Sci 33(1): 62-9. [PMID: 20704601]

Trookman, N. S., R. L. Rizer, et al. (2009). "Immediate and Long-term Clinical Benefits of a Topical Treatment for Facial Lines and Wrinkles." J Clin Aesthet Dermatol 2(3): 38-43. [PMID: 20729942]

Varani, J., R. L. Warner, et al. (2000). "Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin." J Invest Dermatol 114(3): 480-6. [PMID: 10692106]

Velazquez Pereda Mdel, C., C. Dieamant Gde, et al. (2009). "Effect of green Coffea arabica L. seed oil on extracellular matrix components and water-channel expression in in vitro and ex vivo human skin models." J Cosmet Dermatol 8(1): 56-62. [PMID: 19250168]

Yoon, J. H., J. Kim, et al. (2012). "Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts." Biochem Biophys Res Commun 428(3): 416-21. [PMID: 23111328]