Skin cellular youth reprogramming as an innovative anti-ageing strategy for cosmetic ingredient
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Presented by: Marie Meunier
Introduction: It is well-known that several biological mechanisms are affected by the natural ageing of the body, starting from a modification of gene control until visible skin ageing signs. Indeed, ageing cells progressively lose their pluripotency and proliferative capacities, reducing the pool of stem cells which is crucial for the maintenance of skin youth, and leading to an accumulation of non-functional cells throughout life. By losing their pluripotency and functionality, skin cells are losing their skin remodelling driver role among other activities, leading to a progressive apparition of visible ageing signs such as wrinkles, eye-bags or even ageing spots. Taking in consideration this knowledge, we hypothesized that re-activating cell memory to bring back them to pluripotency state appears to be an innovative anti-ageing strategy.
Methods: First, a transcriptomic analysis was performed on normal dermal fibroblasts treated with Terminalia sericea extract at 0.02% for 24 hours to study the impact of the active on several pathways such as antioxidant defences, dermoepidermal junction, extracellular matrix, elastic network, but also cell cycle, proliferation, pluripotency and stem cells. Next, we performed proliferation tests on chemically-induced senescent fibroblasts from a 52 years old donor treated with Terminalia sericea extract at 0.02% up to 72 hours in order to understand how the genes modulation with the active can be a source of rejuvenation for cells. Then, we also wanted to confirm cell rejuvenation by analysing the capacity of cells to synthesize amino acids after 72 hours of treatment with Terminalia sericea extract. To finish, we performed a wide clinical study in order to highlight how Terminalia sericea extract is able to bring a strong anti-ageing benefit thank to cells reprogramming and rejuvenation. For that, a clinical study was conducted on 40 volunteers aged between 35 and 55 years old who had to apply twice daily a cream containing or not Terminalia sericea extract for 4 weeks. Skin elasticity and fatigue were measured with a Cutometer® with R2 and R9 paramaters for elasticity and anti-fatigue respectively. Skin texture and roughness was analysed by DermaTOP-Blue method for a wide anti-ageing effect.
Results: The transcriptomic analysis on fibroblasts evidenced that Terminalia sericea extract significantly upregulated several genes linked to protection and rejuvenation of the extracellular matrix, showing a first potential anti-ageing activity. It also increased the expression of genes involved in cell cycle (+85% MKI67), cell proliferation (+250% IGF1), DNA repair (+56% OGG1), pluripotency transcription factors (+36% NANOG) and stem cells maintenance (+200% SOX2). The analysis of cell proliferation evidenced a significant decrease of proliferation factor for senescent cells compared to young cells by -50%. The treatment with Terminalia sericea extract significantly increased this proliferation factor by +46%, thus senescent cells treated with the active presented a doubling time similar to those of a 22 years old donor. Regarding proteins synthesis, cells were able to synthesise +54% of proteins significantly versus the untreated condition. Through the clinical study, we evidenced the wide anti-ageing effect of Terminalia sericea extract which significantly increased skin elasticity by +20%, reduced skin fatigue by -17% as showed by cutometry. DermaTOP-Blue method evidenced a significant reduction of skin roughness by -10%, translating a soothing effect for Terminalia sericea extract.
Discussion: To resume, Terminalia sericea extract bring a cell rejuvenation regarding transcriptomic analysis by stimulating cell memory leading to the reprogrammation of cell pluripotency. Indeed, our active stimulated the expression of genes such as SOX2, NANOG or C-MYC which is an efficient cocktail for a natural iPS cells reprogrammation. This rejuvenation was confirmed by the significant increase of senescent fibroblasts’ proliferation factor, allowing us estimating a rejuvenation of cells presenting a doubling time equivalent to a 22 years old donor. This huge rejuvenation of fibroblasts’ metabolism was confirmed with an increase of proteins synthesis, reinforcing the set of data showing a rejuvenation of cells with Terminalia sericea extract. With clinical studies, we showed that cells rejuvenation led to a wide anti-ageing efficacy with an improvement of skin elasticity, firmness and reduction of wrinkles and skin fatigue after 28 days of application.
Conclusion: Thanks to this study, we proved that reprogramming cells by stimulating the natural tools available in our DNA is an innovative way to rejuvenate the skin.
Methods: First, a transcriptomic analysis was performed on normal dermal fibroblasts treated with Terminalia sericea extract at 0.02% for 24 hours to study the impact of the active on several pathways such as antioxidant defences, dermoepidermal junction, extracellular matrix, elastic network, but also cell cycle, proliferation, pluripotency and stem cells. Next, we performed proliferation tests on chemically-induced senescent fibroblasts from a 52 years old donor treated with Terminalia sericea extract at 0.02% up to 72 hours in order to understand how the genes modulation with the active can be a source of rejuvenation for cells. Then, we also wanted to confirm cell rejuvenation by analysing the capacity of cells to synthesize amino acids after 72 hours of treatment with Terminalia sericea extract. To finish, we performed a wide clinical study in order to highlight how Terminalia sericea extract is able to bring a strong anti-ageing benefit thank to cells reprogramming and rejuvenation. For that, a clinical study was conducted on 40 volunteers aged between 35 and 55 years old who had to apply twice daily a cream containing or not Terminalia sericea extract for 4 weeks. Skin elasticity and fatigue were measured with a Cutometer® with R2 and R9 paramaters for elasticity and anti-fatigue respectively. Skin texture and roughness was analysed by DermaTOP-Blue method for a wide anti-ageing effect.
Results: The transcriptomic analysis on fibroblasts evidenced that Terminalia sericea extract significantly upregulated several genes linked to protection and rejuvenation of the extracellular matrix, showing a first potential anti-ageing activity. It also increased the expression of genes involved in cell cycle (+85% MKI67), cell proliferation (+250% IGF1), DNA repair (+56% OGG1), pluripotency transcription factors (+36% NANOG) and stem cells maintenance (+200% SOX2). The analysis of cell proliferation evidenced a significant decrease of proliferation factor for senescent cells compared to young cells by -50%. The treatment with Terminalia sericea extract significantly increased this proliferation factor by +46%, thus senescent cells treated with the active presented a doubling time similar to those of a 22 years old donor. Regarding proteins synthesis, cells were able to synthesise +54% of proteins significantly versus the untreated condition. Through the clinical study, we evidenced the wide anti-ageing effect of Terminalia sericea extract which significantly increased skin elasticity by +20%, reduced skin fatigue by -17% as showed by cutometry. DermaTOP-Blue method evidenced a significant reduction of skin roughness by -10%, translating a soothing effect for Terminalia sericea extract.
Discussion: To resume, Terminalia sericea extract bring a cell rejuvenation regarding transcriptomic analysis by stimulating cell memory leading to the reprogrammation of cell pluripotency. Indeed, our active stimulated the expression of genes such as SOX2, NANOG or C-MYC which is an efficient cocktail for a natural iPS cells reprogrammation. This rejuvenation was confirmed by the significant increase of senescent fibroblasts’ proliferation factor, allowing us estimating a rejuvenation of cells presenting a doubling time equivalent to a 22 years old donor. This huge rejuvenation of fibroblasts’ metabolism was confirmed with an increase of proteins synthesis, reinforcing the set of data showing a rejuvenation of cells with Terminalia sericea extract. With clinical studies, we showed that cells rejuvenation led to a wide anti-ageing efficacy with an improvement of skin elasticity, firmness and reduction of wrinkles and skin fatigue after 28 days of application.
Conclusion: Thanks to this study, we proved that reprogramming cells by stimulating the natural tools available in our DNA is an innovative way to rejuvenate the skin.