14:00 - 15:50
Tue-Park Suites-D
Park Suites
Poster Session
Healing the downs of psycho-dermatology
118
Presented by: Elaine Ferreira
Elaine Ferreira, Silvia Pastor, Ariadna Grau-Campistany, Jorge Soriano, Patricia Carulla
Lipotrue, SL., Gava - Barcelona
Telomeres are the DNA-based caps and protein structures located at the end of chromosome tips of eukaryotic cells and are important for cell replication during the lifespan. Telomeres shorten with mitosis, and telomere length is a marker of cellular aging since this complex cell aging system regulates the longevity of cells as well as senescence and apoptosis. Psychological Stress (PS) has emerged as a main influence on telomere detriment that can trigger aging mechanisms.

Diverse studies showed the existence of powerful brain-skin communication since skin has a functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis (HPA) and active neuroendocrine system. The crosstalk between the brain and the skin, under psychological stress (PS), activates HPA axis, among others, that stimulates the release of hormones and neuropeptides, like cortisol and substance P, respectively, that will regulate the stress response. Cortisol is the primary stress hormone in humans and it is necessary for the adaptation to acute stress, but it can be pathogenic over prolonged periods of exposure. Chronic exposure to cortisol is related to shorter telomeres length, late wound healing, reduction of epidermal proliferation and differentiation, impaired permeability barrier, decreased integrity of stratum corneum, diminution of extracellular matrix protein, etc. In this study, we focus on the effect of a Micrococcus ferment lysate (BML_72-4) on the triad among emotional stress-telomer length-skin aging.

This microorganism was sampled from ocean aerosol layers at international waters near Tonga. It was identified by genome sequence and its ferment was characterized by metabolomic studies. It was chosen after high-throughput screenings performed by the Spanish National Cancer Research Center where the effect of several compounds to counteract telomere attrition in vitro was evaluated. This assay was performed measuring the levels of Telomeric Repeat Binding Factor 1 (TRF1), a component of the shelterin complex vital to protect chromosome ends, in CHA9.3 cells using Opera High Content Screening (HCS) system. Subsequently, the capacity of the ferment to protect the DNA from damage was evaluated in primary human keratinocytes (HEK), in presence of H2O2, using 53BP1 as DNA doble strand break marker. The ability of the ferment to recover telomer length was evaluated, by a Dual Quantification qPCR on old vs. young donor fibroblasts. The effect of BML_72-4 on the PS response was analysed in a stressed model of dermis and epidermis where gene expression (qPCR) was evaluated on genes implicated with the PS or affected by it, protein levels of cortisol and keratin 10 (ELISA), nuclear translocation of cortisol receptor (Immunofluorescence) and wound healing (Optical microscopy). Additionally, the effect of BML_72-4 on cortisol-treated skin explants was evaluated by measuring different parameters for Stratum Corneum (SC) quality (Immunohistochemistry and immunofluorescence). In vivo study was performed on 20 Caucasian female volunteers (35-50 years old) showing familiar or work stress and clinical sign of skin aging. A cream containing 2% of the ferment was applied twice a day (half/half method), during 28 days and compared versus placebo. Parameters as wrinkles depth, age-decrease, body skin hydration and elasticity were analysed.

The bacterial ferment increased the levels of TRF1 (+20%), protected DNA of HEK cells from oxidative damage reducing double strand breaks (-71***), recovered the telomer length of old HDF cells versus young cells (+27%). BML_72-4, in a epidermal-stressed model, modulated the expression of several genes implicated in the PS as TAC1(-1.29), IL1b(-1.27) , MMP2(-1.14), MMP9(-1.36), KRT1(+1.16), KRT6(1.13), KRT10 (+1.27) and KRT17(-1.40). Moreover, the ferment reduced the levels of cortisol and avoided the translocation of NR3C1, cortisol receptor, into the nuclei of cells. Furthermore, levels of KRT10(+25%***) and wound healing (+37%***) capacity were recovered. In a dermal-stressed model, BML_72-4 reduced the gene expression of MMP-2 and increased Col1A1(+1.20), Col3A1(+1.15), Col5A1(+1.40) and recovered elastin levels (+15%***). On skin explants treated with cortisol, BML_72-4 recovered SC thickness(+45%***), promoted the increase of corneocyte numbers (+27%***) and decreased SC permeability (-43%***). Through clinical studies, BML_72-4 reduced crow’s feet depth (-13.5%***) showing a quantitative 6-years age reduction, based on this parameter, increased skin hydration(+38.5%***) and elasticity(+8%***) after 28 days.

There are many evidences that PS can be linked with skin physiological aging and according to efficacy studies BML_72-4 is able to act as a novel ingredient in the field of psycho-cosmetics recovering skin allostasis lost with stress.