title: Glyoxalase in ageing.
abstract: The glyoxalase system has been studied since 1913. The biochemical function of this enzymatic system is the metabolism of reactive dicarbonyl metabolites, glyoxal and methylglyoxal, to less reactive products. In the last decade research has shown that methylglyoxal is the precursor of quantitatively important damage to the proteome and genome, forming mainly hydroimidazolone and imidazopurinone adducts in protein and DNA respectively. The aim of this article is to review the evidence of the involvement of the glyoxalase system in ageing and role of glyoxalase in future research into healthy ageing-mainly in mammalian systems for insights into consequences and interventions in human health. Protein and DNA damage by glyoxalase system substrates is linked to dysfunction of proteins susceptible to dicarbonyl modification-the dicarbonyl proteome, and DNA instability and mutation. A component of the glyoxalase system, glyoxalase 1, is a gene with expression influential on lifespan-increasing longevity being associated with increased expression of glyoxalase 1. The glyoxalase 1 gene is also a site of copy number variation in both transcribed and non-transcribed regions giving rise to population variation of expression. The glyoxalase system and Glo1 expression particularly is therefore likely linked to healthy ageing.
authors.affiliation: Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK. Mingzhan.Xue@warwick.ac.uk
authors.forename: Mingzhan
authors.initials: M
authors.lastname: Xue
authors.forename: Naila
authors.initials: N
authors.lastname: Rabbani
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D000375:Aging; D000818:Animals; D031204:Caloric Restriction; D018628:Gene Dosage; D006037:Glyoxal / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D006037:Glyoxal; D007791:Lactoylglutathione Lyase; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase