Isolated Botanical Polyphenol Actin-Binding Compounds Impact Human Dermal Fibroblast Morphology: Potential Anti-Aging Effects and Insight Into YAP/TAZ Mechanical Cytoskeletal Modulation

Abstract

Aging happens to everyone. Coupled with a multi-billion dollar industry, it’s no secret that aging is something that each and every one of us wishes to delay or avoid entirely. The skin is the largest human organ. The extracellular matrix (ECM), which is localized below the outer surface of the skin, provides strength and resiliency and is a major determinant of skin health. The ECM is produced by cells called fibroblasts. Fibroblasts attach to the ECM and this attachment allows fibroblasts to stretch. During aging, structural proteins that make up the ECM, such as type 1 collagen and fibronectin, are degraded through various cell signaling mechanisms. This degradation alters the mechanical properties of the ECM and impairs fibroblast attachment. With loss of attachment, fibroblasts become smaller (collapse) and acquire an aged phenotype. These processes lead to the most common markers of aging, including wrinkles, laxity, and carcinomas. The research described in this thesis focuses on how ECM mechanical properties (i.e. stiffness) and treatment with botanical polyphenol compounds impact fibroblast morphology. The data demonstrate that some of the compounds alter fibroblast morphology through modulation of actin polymerization. Additional data are presented regarding the impact of the botanical compounds on fibroblast function using the mechano-sensitive transcriptional coactivator Yes-associated protein (YAP) as a marker.