Modulating shelterin components at telomere end exhibits antiaging effects: In vivo study
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P7033 In vitro skin structure benefits produced by an olive derivative Rosemarie Osborne, PhD, Procter and Gamble Beauty, Cincinnati, OH, United States; Deborah Finlay, PhD, Procter and Gamble Beauty, Cincinnati, OH, United States; Lisa Mullins, MS, Procter and Gamble Beauty, Cincinnati, OH, United States Background: Signs of skin aging are caused in part by a reduced capacity to rejuvenate skin structure because of cellular damage from reactive oxygen species (ROS) from intrinsic, UV radiation, or environmental sources. We have identified an olive derived material that increases the antioxidant capacity of skin cells regulated by the antioxidant response element (ARE). The goal of the current work was to determine if the olive derived material also can affect the function of skin cells related to production of structural proteins. Methods: Three-dimensional in vitro human skin models evaluated included tissue- engineered skin equivalents (MatTek EFT 400) containing stratified epidermis and dermis and skin explants. The models were treated with the olive derivative (olive oilederived fatty acids modified with PEG-7) for 1 or 7 days, respectively. Levels of expression of skin biomarkers were measured using RT-PCR for mRNA, and ELISA for proteins and hyaluronic acid. Biomarker results were compared to concurrent vehicle controls. Results: The olive derivative significantly stimulated production of procollagen- 1 and hyaluronic acid when applied topically in human skin equivalent cultures. In human skin explants, the material also stimulated production of components and enzymes related to dermal matrix (collagens I and III, elastin, fibrillin-1, LOXL 1 and 2, and tenascin XB) and basement membrane (collagen IV, laminin 5). These effects were significant (P \.05) compared to concurrent vehicle controls. Supported by Procter and Gamble Beauty. P6549 In vivo benefits of a compound that modulates basal epidermal niche components during aging or following solar stress Gilles Oberto, Ashland, Sophia Antipolis, France; Arlette Berghi, Ashland, Sophia Antipolis, France; Karine Cucumel, Ashland, Sophia Antipolis, France; Nouha Domloge, MD, Ashland, Sophia Antipolis, France; Yolene Guerif-Ferreira, Ashland, Sophia Antipolis, France The constant renewal of cutaneous epidermis is supported by cellular proliferation and differentiation of specialized somatic stem cells located in the basal epidermal layer. Somatic stem cells are immersed in a particular environment called the ‘‘niche,’’ whichallows the maintenance of their stemness features: basal epidermal localization, anchorage to the basement membrane, and great proliferative potential for epidermal self-renewal. During aging or after stress, the niche grows lesser as lower levels of basal layer/basement membrane proteins are expressed. The epidermis renewal is slowing down, leading to diminished protective barrier function. For this purpose we designed a compound, IV08.009, that allows maintaining the expression of these proteins (study in vitro) and restoring a correct stemness potential. In the present work, IV08.009 was clinically tested, in order to confirm the benefit in vivo. Two different double-blind studies were conducted. We first evaluated in vivo the skin benefits to modulate basal epidermal niche environment in unstressed condition (first clinical study). The protective effect of IV08.009 was then evaluated in a second clinical study after solar spectrum exposure. For both, the morphologic skin changes were monitoring by in vivo confocal microscopy (VivaScope 1500). Briefly, we showed that the number of active dermal papillae, after formulated IV08.009 application for 28 days, increased by 5 times, whereas the number of functional papillae either in the placebo or the untreated side remained unchanged. In the stressed conditions, we observed significant signs of stress on the placebo side, such as an increase of epidermal thickness, disorganized granular and spinous layers, and numbers of sunburn cells. In contrast, with the IV08.009 treated side, granular cells remained unstressed, granular layer exhibited a good morphology, and we observed a highly significant reduction in the number of sunburn cells. All these results confirmed that the maintenance and the protection of the stemness potential is a key interest in skin protection and skin aging. Commercial support: None identified. P7036 Long term efficacy after use of a sonic applicator using a variety of commercially available eye products Nina Koski, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States; Emily Henes, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States; Greg Peterson, PhD, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States; Katherine Ortblad, MBA, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States; Lauri Tadlock, MD, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States; Michael Kearney, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States Background: Eye serums/creams may be applied to the delicate under-eye area using a gentle tapping motion of the ring finger or using a new novel sonic applicator (SA). The SA generates gentle sonic pulses that rapidly (but gently) applies eye serums/creams (ESC) to outer most layers of the stratum corneum. The purpose of this study was to clinically assess efficacy and safety of the SA when used with commercially available ESC. Measurements of skin hydration (H), user perception (questionnaire), and before/after use photographs were used to assess efficacy and safety. Methods: The SA using commercially available ESC were evaluated in a parallel arm, blinded, randomized 8-week study. Women with visible signs associated with aging between the ages of 35 and 65 (n ¼ 163), participated in a 3-visit study. Subjects were randomized to 1 of 5 leading cosmetic ESC to be used with the SA during the study. All study ESCs were packaged in plain containers, and the subjects were blinded to the ESC assigned for use with the SA. At baseline, the study examiner used the SA to apply the randomized ESC to the left under-eye area for 30 seconds. Subjects used the SA to apply the ESC to the right under-eye area for 30 seconds. H (Corneometer) was measured at baseline (before and15 minutes after product use). Photographs and completion of a questionnaire were obtained to assess efficacy and safety. Subjects were instructed to use the SA/ESC at home twice per day (morning/bedtime). Results: Results for H were compared statistically using a paired t test. A statistically significant increase (P \.05) in H was measured after 15 minutes of use in 4 of the 5 ESC and majority of subjects perceived their skin was more hydrated ( $ 90%) in areas where the ESC was applied after 15 minutes of use. After 8 weeks of use, a majority of subjects perceived their skin had a reduction in fine lines/wrinkles ( $ 76%), more elasticity or firmness ( $ 61%), and healthier looking skin ( $ 74%) in areas where the ESC was applied with the SA. Conclusion: Results from this study confirm efficacy and safety of the SA when used with commercially available ESC. Safety results were confirmed by a separated study conducted by an independent dermatologist and ophthalmologist. 100% sponsored by Pacific Bioscience Laboratories. P6557 Modulating shelterin components at telomere end exhibits antiaging effects: In vivo study Karine Cucumel, PhD, Ashland, Sophia Antipolis, France; Arlette Berghi, Ashland, Sophia Antipolis, France; Deruddre Karine, Ashland, Sophia Antipolis, France; Frederique Portolan, Phd, Ashland, Sophia Antipolis, France; Gilles Oberto, Ashland, Sophia Antipolis, France; Nouha Domloge, MD, Ashland, Sophia Antipolis, France; Yolene Gu erif-Ferreira, Ashland, Sophia Antipolis, France Telomeres are natural and protective regions of repetitive DNA at the end of chromosomes. Maintenance of the level of both shelterin proteins (such as TRF2: telomeric-repeat binding factor-2) and telomere integrity is critical during skin aging. For this purpose, we designed a new compound (IV10.008) that targets shelterin components in vitro. In the present work, IV10.008 was clinically tested in order to confirm the benefit in vivo. A double-blind study was conducted during summertime to evaluate the effect of IV10.008 in counteracting aging effects. During 2 months, volunteers applied on the arm and on the face, twice a day, the IV10.008 cream at 1% and placebo cream. On the arm, after 8 weeks of the inducer-containing cream application, the hydration increased significantly compared to placebo. The VivaScope results showed a preservation of the horny and epidermal layer with good cells morphology and cohesion. The increase of the epidermal thickness of these 2 layers induced by the stress was significantly limited for the IV10.008-treated side compared to placebo. Moreover, we assayed cell density and confirmed what it was shown above, because we noticed a better organization and smaller cells in the granular cell layers. These results were supported by the study on the face, where we noticed a skin less aggressed by summertime condition. The increase, for the wrinkle parameters, of the crow’s feet were less important for the IV10.008-treated side compared to placebo. Because summertime is a challenging period for the skin (sun, sea water, and air dryness), the epidermis thickness and wrinkle parameters increased. However, all these stresses were significantly limited by IV10.008 applications. In conclusion, skin aging can be limited by protecting Shelterin components which seem essential for cellular longevity and functioning. Commercial support: None identified. APRIL 2013 JAM ACAD DERMATOL AB31
Transcript of Modulating shelterin components at telomere end exhibits antiaging effects: In vivo study
P7033In vitro skin structure benefits produced by an olive derivative
Rosemarie Osborne, PhD, Procter and Gamble Beauty, Cincinnati, OH, UnitedStates; Deborah Finlay, PhD, Procter and Gamble Beauty, Cincinnati, OH,United States; Lisa Mullins, MS, Procter and Gamble Beauty, Cincinnati, OH,United States
Background: Signs of skin aging are caused in part by a reduced capacity torejuvenate skin structure because of cellular damage from reactive oxygen species(ROS) from intrinsic, UV radiation, or environmental sources. We have identified anolive derived material that increases the antioxidant capacity of skin cells regulatedby the antioxidant response element (ARE). The goal of the current work was todetermine if the olive derived material also can affect the function of skin cellsrelated to production of structural proteins.
Methods: Three-dimensional in vitro human skin models evaluated included tissue-engineered skin equivalents (MatTek EFT 400) containing stratified epidermis anddermis and skin explants. The models were treated with the olive derivative (oliveoilederived fatty acids modified with PEG-7) for 1 or 7 days, respectively. Levels ofexpression of skin biomarkersweremeasured using RT-PCR for mRNA, and ELISA forproteins and hyaluronic acid. Biomarker results were compared to concurrentvehicle controls.
Results: The olive derivative significantly stimulated production of procollagen-1 and hyaluronic acid when applied topically in human skin equivalent cultures. Inhuman skin explants, the material also stimulated production of components andenzymes related to dermal matrix (collagens I and III, elastin, fibrillin-1, LOXL 1 and2, and tenascin XB) and basement membrane (collagen IV, laminin 5). These effectswere significant (P\.05) compared to concurrent vehicle controls.
APRIL 20
d by Procter and Gamble Beauty.
SupporteP6549In vivo benefits of a compound that modulates basal epidermal nichecomponents during aging or following solar stress
Gilles Oberto, Ashland, Sophia Antipolis, France; Arlette Berghi, Ashland, SophiaAntipolis, France; Karine Cucumel, Ashland, Sophia Antipolis, France; NouhaDomloge, MD, Ashland, Sophia Antipolis, France; Yolene Guerif-Ferreira,Ashland, Sophia Antipolis, France
The constant renewal of cutaneous epidermis is supported by cellular proliferationand differentiation of specialized somatic stem cells located in the basal epidermallayer. Somatic stem cells are immersed in a particular environment called the‘‘niche,’’ which allows the maintenance of their stemness features: basal epidermallocalization, anchorage to the basement membrane, and great proliferative potentialfor epidermal self-renewal. During aging or after stress, the niche grows lesser aslower levels of basal layer/basement membrane proteins are expressed. Theepidermis renewal is slowing down, leading to diminished protective barrierfunction. For this purpose we designed a compound, IV08.009, that allowsmaintaining the expression of these proteins (study in vitro) and restoring a correctstemness potential. In the present work, IV08.009 was clinically tested, in order toconfirm the benefit in vivo. Two different double-blind studies were conducted. Wefirst evaluated in vivo the skin benefits to modulate basal epidermal nicheenvironment in unstressed condition (first clinical study). The protective effect ofIV08.009 was then evaluated in a second clinical study after solar spectrumexposure. For both, the morphologic skin changes were monitoring by in vivoconfocal microscopy (VivaScope 1500). Briefly, we showed that the number ofactive dermal papillae, after formulated IV08.009 application for 28 days, increasedby 5 times, whereas the number of functional papillae either in the placebo or theuntreated side remained unchanged. In the stressed conditions, we observedsignificant signs of stress on the placebo side, such as an increase of epidermalthickness, disorganized granular and spinous layers, and numbers of sunburn cells.In contrast, with the IV08.009 treated side, granular cells remained unstressed,granular layer exhibited a good morphology, and we observed a highly significantreduction in the number of sunburn cells. All these results confirmed that themaintenance and the protection of the stemness potential is a key interest in skinprotection and skin aging.
cial support: None identified.
Commer13
P7036Long term efficacy after use of a sonic applicator using a variety ofcommercially available eye products
Nina Koski, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States;Emily Henes, Pacific Bioscience Laboratories, Inc, Redmond, WA, United States;Greg Peterson, PhD, Pacific Bioscience Laboratories, Inc, Redmond, WA, UnitedStates; Katherine Ortblad, MBA, Pacific Bioscience Laboratories, Inc, Redmond,WA, United States; Lauri Tadlock, MD, Pacific Bioscience Laboratories, Inc,Redmond, WA, United States; Michael Kearney, Pacific Bioscience Laboratories,Inc, Redmond, WA, United States
Background: Eye serums/creamsmay be applied to the delicate under-eye area usinga gentle tapping motion of the ring finger or using a new novel sonic applicator (SA).The SA generates gentle sonic pulses that rapidly (but gently) applies eyeserums/creams (ESC) to outer most layers of the stratum corneum. The purposeof this study was to clinically assess efficacy and safety of the SA when used withcommercially available ESC. Measurements of skin hydration (H), user perception(questionnaire), and before/after use photographs were used to assess efficacy andsafety.
Methods: The SA using commercially available ESC were evaluated in a parallel arm,blinded, randomized 8-week study. Women with visible signs associated with agingbetween the ages of 35 and 65 (n ¼ 163), participated in a 3-visit study. Subjectswere randomized to 1 of 5 leading cosmetic ESC to be used with the SA during thestudy. All study ESCs were packaged in plain containers, and the subjects wereblinded to the ESC assigned for usewith the SA. At baseline, the study examiner usedthe SA to apply the randomized ESC to the left under-eye area for 30 seconds.Subjects used the SA to apply the ESC to the right under-eye area for 30 seconds. H(Corneometer) was measured at baseline (before and15 minutes after product use).Photographs and completion of a questionnaire were obtained to assess efficacy andsafety. Subjects were instructed to use the SA/ESC at home twice per day(morning/bedtime).
Results: Results for H were compared statistically using a paired t test. A statisticallysignificant increase (P\.05) in H was measured after 15 minutes of use in 4 of the 5ESC and majority of subjects perceived their skin was more hydrated ($ 90%) inareas where the ESC was applied after 15 minutes of use. After 8 weeks of use, amajority of subjects perceived their skin had a reduction in fine lines/wrinkles($ 76%), more elasticity or firmness ($ 61%), and healthier looking skin ($ 74%) inareas where the ESC was applied with the SA.
Conclusion: Results from this study confirm efficacy and safety of the SAwhen usedwith commercially available ESC. Safety results were confirmed by a separated studyconducted by an independent dermatologist and ophthalmologist.
nsored by Pacific Bioscience Laboratories.
100% spoP6557Modulating shelterin components at telomere end exhibits antiagingeffects: In vivo study
Karine Cucumel, PhD, Ashland, Sophia Antipolis, France; Arlette Berghi,Ashland, Sophia Antipolis, France; Deruddre Karine, Ashland, Sophia Antipolis,France; Frederique Portolan, Phd, Ashland, Sophia Antipolis, France; GillesOberto, Ashland, Sophia Antipolis, France; Nouha Domloge, MD, Ashland, SophiaAntipolis, France; Yolene Gu�erif-Ferreira, Ashland, Sophia Antipolis, France
Telomeres are natural and protective regions of repetitive DNA at the end ofchromosomes. Maintenance of the level of both shelterin proteins (such as TRF2:telomeric-repeat binding factor-2) and telomere integrity is critical during skinaging. For this purpose, we designed a new compound (IV10.008) that targetsshelterin components in vitro. In the present work, IV10.008 was clinically testedin order to confirm the benefit in vivo. A double-blind study was conductedduring summertime to evaluate the effect of IV10.008 in counteracting agingeffects. During 2 months, volunteers applied on the arm and on the face, twice aday, the IV10.008 cream at 1% and placebo cream. On the arm, after 8 weeks ofthe inducer-containing cream application, the hydration increased significantlycompared to placebo. The VivaScope results showed a preservation of the hornyand epidermal layer with good cells morphology and cohesion. The increase ofthe epidermal thickness of these 2 layers induced by the stress was significantlylimited for the IV10.008-treated side compared to placebo. Moreover, we assayedcell density and confirmed what it was shown above, because we noticed a betterorganization and smaller cells in the granular cell layers. These results weresupported by the study on the face, where we noticed a skin less aggressed bysummertime condition. The increase, for the wrinkle parameters, of the crow’sfeet were less important for the IV10.008-treated side compared to placebo.Because summertime is a challenging period for the skin (sun, sea water, and airdryness), the epidermis thickness and wrinkle parameters increased. However, allthese stresses were significantly limited by IV10.008 applications. In conclusion,skin aging can be limited by protecting Shelterin components which seemessential for cellular longevity and functioning.
cial support: None identified.
CommerJ AM ACAD DERMATOL AB31
