老化科学ジャーナル

概要

Vulnerability of Human Erythrocytes to Persistent High Glycemic Index Diets: Implications for Ageing and Neurodegeneration: Possible Amelioration by Carnosine

Alan R Hipkiss

It is proposed that excessive consumption of high carbohydrate and high glycemic index (GI) diets, typical of the socalled Western diet, converts human erythrocytes into systemic sources of methylglyoxal (MG) and glycated protein, including alpha-synuclein. This is due to activity-induced deamidation of asparagine residues in the glycolytic enzyme triosephosphate isomerase (TPI), which can result in loss of enzyme activity and accumulation of the MG precursor dihydroxyacetone-phosphate. Under such circumstances, erythrocytic MG could provoke protein glycation in the tissues, including the brain, and may be responsible for much age-associated macromolecular modification. The naturally-occurring and pluripotent dipeptide carnosine (beta-alanyl-L-histidine) is enriched in erythrocytes (10-fold compared to sera). Carnosine could help to ameliorate MG generation and reactivity, due to its ability to (i) partially inhibit glycolysis and suppress MG generation and (ii) prevent MG-induced protein glycation, It is concluded that persistent consumption of high GI diets should be avoided, and carnosine, administered orally or intra-nasally to enhance access to the brain, could be explored with respect to age-related conditions including type-2 diabetes and neurodegeneration.