Dicarbonyl-Induced Accelerated Aging in Human Skin Fibroblasts

Abstract

Dicarbonyls glyoxal (GO) and methylglyoxal (MGO) produced during the autoxidation of reducing sugars can be a source of macromolecular damage in the cells. We have studied the effects of GO and MGO on the induction of protein oxidative damage and accelerated senescence in normal human skin fibroblasts. A treatment of cells with 1.0 mM glyoxal (GO) or 400 μM methylglyoxal (MGO) leads to the appearance of senescent phenotype within 3 days by the following criteria: morphological phenotype, irreversible growth arrest and G₂ arrest, increased senescence-associated β-gal activity, increased H₂O₂ level, increased Nξ-(carboxymethyl)-lysine (CML) protein level, and altered activities of superoxide dismutase and catalase antioxidant enzymes. This experimental model of accelerated aging can be useful for studies on testing the effects of various physical, chemical and biological conditions, including natural and synthetic molecules, for the modulation of cellular aging in vitro.