Methylglyoxal (MGO)
Methylglyoxal (MGO) is a highly reactive, damaging molecule (a dicarbonyl) that your cells make as an accidental byproduct of glycolysis (sugar-burning). It is the main home-grown source of advanced glycation end products (AGEs). It reacts with arginine in proteins to form adducts (mainly one called MG-H1), and with lysine to crosslink proteins. Your cells detoxify it with the glyoxalase system. The enzyme GLO1 converts MGO into an intermediate, and GLO2 then turns that into D-lactate. When this system cannot keep up, MGO builds to harmful levels, a state called 'dicarbonyl stress'. GLO1 activity falls with age in worms and rodents. And in humans, low GLO1 activity tracks with high blood MG-H1, though the link is still associational. Chronically high MGO damages your proteins, DNA, and lipids, switches on NF-κB and p38 MAPK, and harms mitochondria. That ties dicarbonyl stress to diabetes, heart disease, and neurodegeneration. The standard biomarker is MG-H1 in blood or urine. And drugs to boost GLO1 or scavenge MGO are still experimental as of 2025.
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Sources
- Schalkwijk CG, Stehouwer CDA. (2020). Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases. Physiological Reviewsdoi:10.1152/physrev.00001.2019
- Rabbani N, Xue M, Thornalley PJ. (2016). Methylglyoxal-induced dicarbonyl stress in aging and disease: first steps towards glyoxalase 1-based treatments. Clinical Sciencedoi:10.1042/CS20160025
- Nigro C, Leone A, Fiory F, et al. (2019). Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging. Cellsdoi:10.3390/cells8070749