Exploring senescence-related factors to combat skin aging

Summary: Abstract Body: Cellular senescence is part of the twelve Hallmarks of aging and is largely addressed nowadays to delay skin aging. The increase of stress and decrease in cell proliferation are recognized as key factors in senescence. Senescence is in part associated with an upregulation of pro-inflammatory cytokines (IL-6 and IL-8), mediated by retinoic-acid-inducible gene-I (RIG-I). Interestingly Klotho, a cofactor of the FGF receptor, has been found to suppress RIG-I-mediated inflammation, suggesting its role as an intracellular anti-inflammatory and anti-aging factor. Besides Progerin, a truncated version of Lamin A, impairs DNA damage repair leading to premature cellular senescence. Targeting these two factors with a natural Dill extract, holds promise as a specific cosmetic approach to delay cell senescence and, consequently, skin aging. In vitro experiments involved assessing Progerin synthesis in fibroblasts using ELISA method, with insulin as a positive control. Immunofluorescence was used to evaluate Klotho synthesis in a fibroblast culture, while IL-6 expression was assessed in keratinocytes after LPS stress. Results showed on fibroblasts that Dill extract significantly reduced the accumulation of Progerin by up to 54% and increased the level of Klotho protein by up to +34%. Notably, Dill extract also decreased IL-6 secretion after stress. A clinical study was finally conducted, evaluating the anti-wrinkle effect on crow's feet through digital image analysis, assessing skin biomechanical properties using cutometry, and clinical scoring of skin elasticity and jawline slackness. After three months of applying Dill extract, features of skin aging linked to senescence were significantly improved. These effects were measurable, visible, and perceivable by the volunteers. This study highlights the significance of targeting Progerin and Klotho-related biological pathways to slow-down skin aging and paves the way for new antisenescence targets. Philip Ludwig¹, Sabrina Leoty-okombi², Valérie André² 1. BASF Corp Tarrytown, Tarrytown, NY, United States. 2. BASF Beauty Care Solutions France SAS, Lyon, Auvergne-Rhône-Alpes , France. Cell Communication Networks and Stromal Biology