Fructose-Induced Glycation End Products Promote Skin-Aging Phenotypes and Senescence Marker Expression in Human Dermal Fibroblasts

Skin aging is a multi-factorial process characterized by the progressive deterioration of biomechanical properties and cellular functionality. One such factor is the formation of advanced glycation end products (AGEs), which are known to have detrimental effects on the skin, including stiffening of the extracellular matrix (ECM) and reduction of cellular proliferation. AGEs accumulate because of sugar metabolism dysfunction; however, the direct impact of elevated sugar levels on cellular physiology requires further investigation. Here, we elucidated the effects of elevated fructose levels on skin cell function using in vitro models and hypothesized that high fructose levels adversely impact cell function. By fluorescence microscopy, we observed that high fructose induced different cellularity, cell morphology, and stress fiber appearance than the controls. Skin cells exposed to high fructose levels showed impaired growth and delayed closure in an artificial wound model. Mechanistically, high fructose conditions induce inflammatory cytokines and activate the NFκB pathway. Furthermore, we observed for the first time an increase in the senescence markers p16, p21, and p53 in response to high fructose levels. Taken together, we show that high fructose levels affect many critical skin functions that contribute to the aging process and recapitulate several aspects of aging related to AGEs.