GLP-1RA and the possible skin aging.

Area of Science:

• Dermatology
• Endocrinology
• Molecular Biology

Background:

• Glucagon-like peptide 1 receptor agonists (GLP-1RA) are used for type 2 diabetes mellitus (T2DM) and obesity.
• Patients report "Ozempic face" and facial aging as side effects of GLP-1RA therapy.
• While GLP-1RA can reduce inflammation and potentially benefit skin, weight loss is not the sole cause of facial aging.

Purpose of the Study:

• To review existing literature on the mechanisms by which GLP-1RA may influence skin aging.
• To explore the direct and indirect effects of GLP-1RA on skin cells and aging processes.
• To elucidate the pathophysiology behind "Ozempic face" beyond simple fat reduction.

Main Methods:

• Literature review of studies investigating GLP-1RA effects on skin cells.
• Analysis of data on GLP-1R expression in adipose-derived stem cells (ADSC) and fibroblasts.
• Examination of molecular pathways including cytokine production, oxidative stress, ATP synthesis, and estrogen levels.

Main Results:

• GLP-1RA stimulation of GLP-1R on ADSCs reduces protective cytokine production, increasing reactive oxygen species (ROS) and oxidative damage to fibroblasts.
• GLP-1RA decreases glucose uptake by ADSCs, leading to reduced ATP production and apoptosis.
• GLP-1RA indirectly lowers estrogen production in dermal white adipose tissue (DWAT), decreasing fibroblast collagen synthesis.
• GLP-1RA interacts with advanced glycation end products (AGEs) and RAGE activation, contributing to skin aging.

Conclusions:

• "Ozempic face" and facial aging are common side effects of GLP-1RA therapy.
• These effects are multifactorial, involving direct impacts on ADSCs and fibroblasts, oxidative stress, and hormonal changes.
• Mechanisms beyond fat loss contribute significantly to GLP-1RA-induced skin aging, requiring further elucidation.