Accueil du site > Equipes > Fonctionnalité et dynamique du tissu cutané (D. Sigaudo-Roussel) > Thématiques > Signature épigénétique du vieillissement et de la sensibilité cutanée au stress
Project leader : Jérôme Lamartine
Colleagues involved in the project : Charlotte Muther, Taku Nedachi, Kevin Terretaz, Joshua Dulong, Jérôme Lamartine
ncRNAgingSKIN : Non-coding RNAs in skin aging, identification and functional exploration of potential new targets for skin rejuvenation
During the natural aging process, the skin undergoes a physiological deterioration caused by progressive changes in genetic and metabolic processes. A better understanding of these endogenous pathways progressively disturbed by aging is required to identify new biomarkers of aged skin and to propose strategies for skin rejuvenation. To that aim, we are focusing on non-coding RNAs (microRNAs and large intergenic non-coding RNAs, lncRNAs) that represent important regulators of gene networks, especially in skin.
We want to identify new non-coding RNAs (ncRNAs) potentially deregulated in skin aging, to address their function in cutaneous physiology and to develop efficient strategies to counteract or delay their deleterious action during aging. We settled up an extensive screening of ncRNAs that are differentially expressed in chronological aging (young vs aged skin samples). The second part of the study will aim to decipher the function of these age-related ncRNAs in epidermal homeostasis. These candidate ncRNAs will be inactivated in cultured epidermal cells and reconstructed skin and will assess different parameters of cellular physiology. This step of the study should bring new insights into the function of these age-modulated ncRNAs in epidermal homeostasis and will also provide potential new anti-aging strategies.
Hierarchical clustering of ncRNA expression within young and old skin samples. Red : over-expressed ncRNAs. Green : down-expressed ncRNAs
EPISENSRAD : EPIgenetic signature of cutaneous SENSitivity to ionizing RADiations
Skin is a target organ and a possible indicator of exposure to external stresses. The individual sensitivity to genotoxic stresses is highly variable among the general population : identifying highly sensible individuals is a crucial issue especially in the case of ionizing radiations (IR) to prevent the secondary effects of radiotherapy. Moreover, the molecular and cellular bases of radio-sensitivity remain poorly understood. To go forward into these 2 goals, we are settling up a research project based on a human model of radiation sensitivity, the Gorlin syndrome, a rare cancer-prone genetic disease. Gorlin patients exhibit a very high cutaneous radio-sensitivity. Genome-wide expression and methylation studies allowed us to identify specific expression and methylation pattern of Gorlin patient’s fibroblasts. Based on these data, we extend now this study to other types of radiosensitive patients in order to establish a representative epigenetic signature of individual radiosensitivity in cutaneous tissues. This will pave the way to the development of diagnostic tests usable for identifying at-risk individuals. We will also investigate the molecular basis of this phenotype by functional studies of gene networks up- or down-regulated in fibroblasts and keratinocytes from radiosensitive individuals. Our strategy will be also transferable to other environmental stresses such as UV, chemicals or nanoparticles, where the identification of sensible individuals will probably represent an important issue in the forthcoming years.