Dicarbonyl-Induced Accelerated Aging in Human Cells

In my master’s thesis I studied the effects of dicarbonyls glyoxal (GO) and methylglyoxal (MGO) on the induction of protein oxidative damage and accelerated aging in normal human skin fibroblasts. An imbalance in the intracellular glucose metabolism leads to increased levels of its oxidative breakdown products such as the dicarbonyls GO and MGO. The dicarbonyls attack the amino groups of proteins, nucleotides and lipids with their highly reactive carbonyl groups. Thus, intracellular proteins accumulate glycation adducts during aging. Many age-related pathologies, including Alzheimer´s disease and diabetes, are associated with the accumulation of altered proteins.

My lab results show that a treatment of cells with 1.0 mM GO or 400 μM 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 hydrogen peroxide level, increased 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.

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