LONGECITY

 

Methylglyoxal (MG) is a side-product of mainly glycolysis that together with reactive oxygen species (ROS) leads to cellular dysregulation in age-related diseases and is a potential causal factor behind diabetes.

 

The glyoxalase system is the most important system in the metabolism of MG, but evidence indicates that other enzymes also play an important role in regulating MG levels.

Although involved in cellular dysregulation, mild MG stress also enhances lifespan in model organisms via a hormetic response.

MG levels can be modulated with small molecules in vivo targeting glycolytic enzymes as well as genes under the control of the antistress response elements (AREs), pointing to novel therapeutic targets.

 

Methylglyoxal (MG) is a ubiquitous metabolite that spontaneously reacts with biopolymers forming advanced glycation end-products (AGEs). AGEs are strongly associated with aging-related diseases, including cancer, neurodegenerative diseases, and diabetes. As the formation of AGEs is nonenzymatic, the damage caused by MG and AGEs has been regarded as unspecific. This may have resulted in the field generally been regarded as unappealing by many researchers, as detailed mechanisms have been difficult to probe. However, accumulating evidence highlighting the importance of MG in human metabolism and disease, as well as data revealing how MG can elicit its signaling function via specific protein AGEs, could change the current mindset, accelerating the field to the forefront of future research.