Diabetes and Cannabinoid CB1 receptor deficiency promotes similar early onset aging-like changes in the skin

Background: The cannabinoid receptor type-1 (CB₁R) is a major regulator of metabolism, growth and inflammation. Yet, its potential role in the skin is not well understood. Our aim was to evaluate the role of CB₁R in aging-like diabetic skin changes by using a CB₁R knockout mouse model.

Methods: We evaluated several signals of skin aging in wild-type control (WT), WT streptozotocin-induced type 1 diabetic mice (WT DM), CB₁R knockout (CB₁RKO) and CB₁RKO DM mice. We quantified markers of inflammation, angiogenesis, antioxidant enzymes and collagen content. Moreover, we evaluate reactive oxygen species (ROS) levels and macrophage phenotype, M1 and M2.

Results: CB₁R expression is decreased in the skin of WT DM mice and collagen levels are decreased in the skin of WT DM, CB₁RKO and CB₁RKO DM mice. Additionally, the absence of CB₁R correlated with higher expression of pro-inflammatory markers, also evident in WT DM or CB₁RKO DM mice. Moreover, the M1/M2 macrophage ratio and ROS levels were significantly elevated but in the diabetic WT and the CB₁RKO mice, consistent with a significant decrease in the antioxidant capacity of the skin.

Conclusions: Our results indicate that CB₁R deficiency in the skin may lead to accelerated skin aging due to the increased production of ROS, a decrease in the antioxidant defenses and a higher pro-inflammatory environment. A significant decrease in the CB₁R expression may be a significant contributing factor to the early aging-like changes in diabetes.