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The Dermoepidermal Junction as the Initiation Point for Reversal of Dermatoporosis

April 2026 | Volume 25 | Issue 4 | 9777 | Copyright © April 2026


Published online March 30, 2026

Alan D. Widgerow MBBCh MMed FCS FACSa, Orit Markowitz MDb, Jean Carruthers MD FRCSC FRC (Ophth)c, Faiza Shafiq MBBS CCRPa

aGalderma Laboratories, L.P., Dallas, TX
bMarkowitz Medical, New York, NY
cDepartment of Ophthalmology, University of British Columbia, Vancouver, Canada

Abstract
Background: Dermatoporosis (DP) or chronic cutaneous fragility syndrome has traditionally been linked to extracellular matrix (ECM) dehydration, reduced cellular turnover, epidermal thinning, and vascular fragility. However, recent imaging methods and clinical evidence indicate that the dermoepidermal junction (DEJ) might be the earliest change reflecting DP reversal.
Objective: To propose a new mechanistic process in which the DEJ acts as the initiation point for reversing the DP. The process is supported by clinical and imaging evidence, as well as independent literature on DEJ biology.
Methods: A combination of clinical and investigational findings, published theoretical models, and evidence from wound-healing, skin-longevity reports, ex vivo model analyses, and device-based interventions formed the basis for the scientific narrative.
Results: Cumulative evidence suggests that an initial change in the DEJ, along with structural restoration, appears to trigger or initiate regenerative processes in the ECM and epidermis. These include the renewal of basal stem cells following adhesion signaling in the basement membrane; ECM remodeling through improved communication between the dermis and epidermis, along with enhanced fibroblast interactions involving collagen and elastin; and finally, ECM remodeling and stabilization of basement membrane anchoring provides support and stability to blood vessels, protecting them from recurrent injury.
Conclusion: The DEJ acts as a bridge between the epidermis and dermis, providing structural support while also triggering signaling cascades that promote a regenerative environment, contributing to DEJ reversal. Targeting the DEJ could be a logical therapeutic approach, establishing a new paradigm for biomarker analysis and an intervention site for regenerative initiation.

 

INTRODUCTION

Dermatoporosis is a term first coined by Kaya and Saurat in 2007, describing progressive skin thinning, extracellular matrix (ECM) degradation, vascular fragility with resultant purpura, and general vulnerability of the skin.1 The condition likely affects the vast majority of the population, but it usually manifests in the older age group, typically those over 65 years old. It is underrecognized and may be regarded as the equivalent of "osteoporosis of the skin", often starting decades earlier than the manifestation seen in older age groups.

Traditionally, the pathogenesis was regarded as one of ECM deficiency, particularly related to glycosaminoglycans (hyaluronic acid in particular), with decreased cellular turnover.2 More recently, DP has been recognized as associated with a more extensive global ECM degradation, fibroblast senescence, and macrophage dysfunction.3 This ECM degradation affects the structural support of the vasculature, making it more vulnerable to damage and injury.3

A recent clinical trial evaluating regenerative peptides with ECM remodulating activity and marked clinical improvement has demonstrated that the earliest measurable changes appear to be observed in structural changes to the dermoepidermal junction (DEJ), which precede widespread regenerative changes in the ECM and dermis.4 This suggests that the DEJ, rather than being a passive basement membrane providing structural support, may well signal and initiate the regenerative changes seen with DP reversal.

The Dermoepidermal Junction
Examining Structure and Function
The DEJ has long been recognized as a structural anchoring membrane fixing basal keratinocytes to the dermal papillary layer. This structural adhesion aids in limiting shear forces from damaging the junction, distributing these shear forces among the undulating rete pegs seen with a healthy DEJ.5 Flattening of the DEJ with aging, effacement of the structure weakens the adhesive forces, decreases the distribution of shearing forces, and subjects the skin to injury and damage, with a predisposition to tears.3
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