Gorab Deficiency in Skin Dermis Accelerates Aging and Is Associated with Dysregulation of RCHY1-Mediated P53 Ubiquitination

This study investigates the role of Gorab gene deficiency in skin aging, using a dermal Gorab knockout mouse model. The research reveals that Gorab mutations lead to accelerated skin aging by increasing levels of aging-related proteins (P53, P21, P16) and reducing extracellular matrix (ECM) components like collagen and fibronectin. The mechanism involves impaired ubiquitination and accumulation of P53 protein, likely regulated by the E3 ligase RCHY1, along with increased HDAC2 levels and reduced histone acetylation. These changes disrupt ECM expression, highlighting a pathway for accelerated skin aging. The findings enhance understanding of Gorab's role in skin aging and suggest potential preventive strategies.