Within the context of aging, there is an increase in protein damage as a result of non-enzymatic glycation. The formation of advanced glycation endproducts (AGEs) is associated with the development of age-related diseases including hypertension and atherosclerosis and is, at least in part, a likely mechanism accounting for vascular senescence. Protein glycation was viewed originally as a post-translational modification of proteins that accumulated slowly on extracellular and long-lived proteins throughout life. In the extracellular matrix, AGEs caused aberrant cross-linking resulting in a decrease of elasticity in vessels leading to arterial stiffness and hypertension, i.e. hallmarks of vascular ageing. In addition, glycation adducts are also formed in a fast manner on cellular and short-lived extracellular proteins and on DNA. The highly reactive methylglyoxal is a key compound involved in the very fast generation of glycation adducts on proteins, lipids and DNA. Methylglyoxal is mainly generated as a by-product of glycolysis. To counteract the deleterious effects of methylglyoxal, organisms contain an enzymatic glyoxalase defense system comprised of glyoxalase I (GLO1) and GLO2, in which methylgyoxal is converted to D-lactate. GLO1 is a key enzyme in regulating the levels of methylglyoxal and AGEs. In proteins, methylgyoxal reacts mainly with arginine residues to form the non-fluorescent products 5-hydro-5-methylimidazolone (MG-H1) as a major AGE quantitatively. DNA is also susceptible to glycation by methylglyoxal, where the nucleotide deoxyguanosine is most reactive under physiological conditions. Although the biological consequences of methylgyoxal-derived DNA adducts have not yet been fully established, the non-enzymatic glycation of DNA by methylgyoxal may have severe implications for various pathological conditions, such as age-related complications. Several studies showed that there is a decline in the expression of GLO1 with age, which may contribute to increased risk of cardiovascular disease with ageing. Also in the C. elegans it has been shown that activity of GLO1 declines during aging. Overexpressed of the homologue of GLO1 in C.elegans increased mean lifespan and maximum lifespan found by ca. 30% and silencing decreased lifespan by ca. 50%, demonstrating that GLO1 is a gene influential on lifespan. Further studies showed that methylgyoxal-derived AGE accumulation in ageing was localized to mitochondria and were associated with mitochondrial superoxide formation. Similar to C. elegans, also in mammalian cell cultures increased age was associated with decreased GLO1 activity. It was demonstrated that the load of AGE-modified proteins increases during replicative senescence. In rats with type 1 diabetes, overexpression of the GLO1 gene (Glo1) not only counteracts the rise in methylglyoxal, AGEs and oxidative stress, but also prevents the development of endothelial dysfunction, and the microvascular complications retinopathy and of nephropathy. Non-diabetic GLO1-transgenic aged rats showed amelioration of senescence, as assessed by expression levels of senescence markers such as p53 and p16INK4A and senescence-associated β-galactosidase staining, associated with reduction of renal AGEs, interstitial thickening and were protected against age-dependent decline of renal functions. In vitro experiments in cultured endothelial cells showed that knock-down of Glo1 resulted in an increase in markers of endothelial dysfunction and inflammation. Methylglyoxal influences multiple aspects of cellular biology including increased formation of oxidative stress and vascular changes. Moreover, it has been demonstrated that the modification of proteins by methylglyoxal results in increased expression of adhesion molecules, growth factors and a sensitizing of cells to the effects pro-inflammatory cytokines. In conclusion, findings so far suggest that GLO1belongs to the network of genes that influence longevity. The balance between the production of methylglyoxal and its detoxification by GLO1 can significantly contribute to the ageing process and to the onset of vascular ageing.