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    Online Exclusives

    A Shifting Metabolite Impacts Skin

    The Estée Lauder Companies showcases skin metabolomics research at the World Congress of Dermatology.

    A Shifting Metabolite Impacts Skin
    Speakers during an ELC-sponsored symposium entitled, "Metabolomics as a New Diagnostic to Assess Skin Health" included (l-r): Kirk Beebe, senior director, Discovery and Translational Sciences, Metabolon, Inc.; Paolo Sassone-Corsi, director, Center for Epigenetics and Metabolism, University of California, Irvine; Leihong Xiang, MD, PhD. PHOTO: Jacopo Raule by Getty Images for Estée Lauder.
    A Shifting Metabolite Impacts Skin
    Nadine Pernodet, PhD, VP-skin biology and bioactives, research and development, The Estée Lauder Companies. Photo: Jacopo Raule by Getty Images for Estée Lauder.
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    Tom Branna, Editorial Director07.11.19
    Skin metabolomics was front and center at the World Congress of Dermatology last month. The research and development team at Estée Lauder Companies Inc. (ELC) presented data focused on new findings in metabolomics, skin defense, ingredient science, and anti-aging research during the Congress, which was held in Milan.

     
    Additionally, a sponsored symposium, "Metabolomics as a New Diagnostic to Assess Skin Health" took place during the Congress. The symposium unveiled novel metabolomics research illustrating the complex relationship between genetics and the environment, detailing the role they play in skin and how their changes reflect skin's condition. Session chair was Leihong Xiang, MD, PhD. Presenters included Paolo Sassone-Corsi, PhD, University of California, and Kirk Beebe, PhD, Metabolon, Inc.

     
    “ELC has been attending the World Congress of Dermatology for decades. Our presence at this conference ensures that we or our scientific experts are able to hear directly from world-leading dermatologists and researchers to understand the latest in dermatology patient needs and beauty trends,” explained Nadine Pernodet, PhD, VP-skin biology and bioactives, research and development, The Estée Lauder Companies. “As the meeting only occurs once every four years, the WCD also provides ELC both the opportunity to share our latest state-of-the art research with the global scientific community and the ability to meet with potential research collaborators and partners.”

     
    Here’s a summary of ELC’s research that was presented at WCD 2019:
    • Skin metabolomics can help us better understand young and aging skin and the impact of circadian rhythm changes in the human skin metabolome.
    • The relationship between autophagy and inflammation in skin cells, with a look at the link between autophagy and resolution phase, a mechanism in the inflammation process that helps protect the skin against chronic inflammation.
    • Development of a skin model to further understand the causes of post-inflammatory hyperpigmentation (PIH) and how those findings offer more options to explore the underlying biological causes.
    • Macrocystis pyrifera (kelp) ferment is effective in addressing inflammation and in enhancing fibroblast migration. Together these activities may help skin maintain its natural integrity and a state of visible calm.
    • UP302, a plant-derived tyrosinase enzyme inhibitor, acts as a whitening agent to reduce pigmentation, outperforming the benchmark compound, kojic acid, at the industry-standard concentration.
    • There is a beneficial link between sirtuins and maintaining the integrity of natural cellular activity.
    • Examining changes in skin physiology induced by exposure to small particles (PM 2.5) can help inform skin protection against the detrimental effects from the environment.
    • A multi-prong approach to acne treatment significantly reduced facial lesions after a 12-week trial.

     
    ELC scientists have been studying metabolomics for the past five years. According to Pernodet, metabolomics has the ability to capture a precise snapshot of skin condition, reflecting information about the dynamic cellular processes in skin.
     

    “It is therefore a current state, in vivo measurement of the skin surface. Since factors that affect skins’ appearance like genetics, environment and lifestyle alter metabolite levels, ELC is harnessing metabolomics patterns as a direct link to real-time skin condition,” she explained.

     
    ELC researchers were able to show, for the first time, that the skin’s metabolite profile is not fixed, but dynamic and that the profile in young, healthy skin follows a circadian rhythm which is altered in mature skin. This natural rhythm ensures that skin is performing optimal repair and protection processes at the appropriate times. ELC has found that specifically formulated products can shift key metabolites and help mature skin re-establish an ideal rhythm, according to Pernodet.

     
    In its research, ELC is collaborating with Metabolon, which has several advantages for the beauty maker.

     
    “Many companies are doing metabolomics studies (detecting hundreds of metabolites), but the advantage of collaborating with Metabolon is that they have built their metabolites database for many years and have the most experience globally,” observed Pernodet. “Our expertise comes from how to interpret these metabolites as related to skin. Therefore, it makes complete sense we collaborated.”

     
    According to Pernodet, metabolomics studies are going to help ELC and its supply partners on many different levels.

     
    “After finding and identifying new targets, we will connect with our collaborators to develop specific and exclusive actives for us to target these new pathways,” she explained. “We will also use metabolomics studies as a diagnostic to evaluate product performance.”

     
    Of course, the study of metabolomics will ultimately help consumers, too.

     
    “While we have already characterized the metabolomic profiles of healthy young and mature skin, we seek to define metabolomic profiles associated with skin conditions ranging from acne to sensitive skin and more in order to always increase our skin care performance,” Pernodet concluded.

     
    Here are more details on what Estée Lauder presented at the Congress:
    • First assessment of skin circadian metabolomics on young and aging subjects, The Estée Lauder Companies and Metabolon, Inc., [Poster #5638]
    Metabolomics is a comprehensive study of metabolites, which are small molecule (<1500 Da) intermediates and products of biochemical reactions. Using metabolomics, the research was able to temporally define the skin metabolome via assessing circadian rhythm dynamics in the human stratum corneum using non-invasive D-squame collection methods. Results indicated a clear natural rhythm of the young skin metabolome. This study provides further understanding of aging skin and defined the temporal human skin metabolome thus showing circadian rhythm-dependent changes in repair and protection processes in human skin. And finally, this is the first study that shows a treatment can help to skin's natural repair as proven through metabolomics.

     
    •  Autophagy and inflammation relation in skin cells, The Estée Lauder Companies, [Poster #3897]
    Autophagy, a major cellular degradative and recycling pathway, is critical for cellular longevity and has been linked to the aging process. A decrease in autophagy leads to increased cellular damage as we age. For the first time in skin cells, a relationship between autophagy and the resolution phase of inflammation has been found, showing their link in protecting the skin against long-lasting inflammation and its visible effects.
     

    • Development of a post inflammatory hyperpigmentation model in reconstructed skins, The Estée Lauder Companies [Poster #4263]
    Prominently seen in people with darker skin tones, post inflammatory hyperpigmentation (PIH) occurs following an inflammatory insult, such as acne or a cutaneous injury, and results in a hyperpigmented area of the skin. Little is known about the cause of PIH, but new research using in vitro models offers the chance to screen the skin pigmentation effects of migration inhibitors on melanocytes--offering more options to explore the underlying biological causes.
     
     
    • Macrocystis pyrifera ferment: Anti-inflammatory and pro-resolution properties, The Estée Lauder Companies and Max Huber Research Laboratories [Poster #2331]
    Research has shown that inflammation, especially chronic inflammation, is a potential cause of accelerated skin aging. The resolution of inflammation is an actively coordinated and dynamic process that attenuates inflammation and enables skin's natural repair and helps skin maintain its natural integrity. In this study, the anti-inflammatory and pro-resolution activities of the Macrocystis pyrifera (kelp) ferment were assessed. Results show that the use of the kelp ferment is effective in addressing all three phases of inflammation and in enhancing fibroblast migration. Together these activities may help skin maintain a state of visible calm and its natural integrity.
     
     
    • Evaluation of a potent skin whitening agent, The Estée Lauder Companies [Poster #4255]
    UP302, a plant-derived tyrosinase enzyme inhibitor, acts as a whitening agent by preventing melanin synthesis through the conversion of tyrosinase in human skin. Using a clinical whitening test measuring Skin Lightening Factor, both in vitro and in vivo, against Kojic acid (the industry standard), the UP302 treatments demonstrated a more-significant decrease in melanin, indicating a decrease in tyrosinase activity and pigmentation.
     
     
    • Sirtuins and their importance in skin, The Estée Lauder Companies [Poster #3893]
    Increasing evidence has demonstrated the importance of Sirtuins, also known as longevity proteins, in maintaining optimal skin cell processes such as metabolism, genomic stability, inflammation, energy, environmental stress response and aging. The effects of environmental stressors were examined through the response of skin cells to UVB and ozone (measured by the effect on energy (ATP) production and oxidative damage (ROS), along with the effect on mechanical properties). This research demonstrates a beneficial link between sirtuins and cellular integrity and activity, and for the first time, introduces the role of Sirtuin-2 in supporting skin cells' natural mechanical properties.
     
     
    • The effect of exposure to PM 2.5 on skin physiological function, The Estée Lauder Companies [Poster #4260]
    Using an in vitro model, changes in skin physiology induced by exposure to fine particles (PM 2.5) were observed. Results suggested that these particles may be damaging to the epidermis and compromise skin barrier function, as well as impact morphology, physiology, and inflammatory response in cells. Findings showed that skins treated with PM 2.5 had compromised skin barrier integrity and an increase in cellular proteins indicating a possible inflammatory response.
     
     
    • A multi-prong approach to acne significantly reduced facial lesions after a 12-week treatment, The Estée Lauder Companies [Poster #4194]
    The pathogenesis of acne is complex, with strong evidence supporting the involvement of sebaceous hyperplasia, follicular hyperkeratinization, bacterial hypercolonization, and inflammation. In order to combat acne and address these components, researchers used a multi-prong formulation to assess its effect on the overall lesion count in a population with acne. Findings showed treatments significantly reduced the total lesion count after 12 weeks.
     
     
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