Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with proteincarbonyl groups

Carnosine (beta -alanyl-L-histidine) is a physiological dipeptide which can delay ageing and rejuvenate senescent Cultured human fibroblasts. Carnosin e's anti-oxidant. free radical- and metal ion-scavenging activities cannot adequately explain these effects. Previous Studies showed that carnosine re acts with small carbonyl compounds (aldehydes and ketones) and protects mac romolecules against their cross-linking actions. Ageing is associated with accumulation of carbonyl groups on proteins. We consider here whether carno sine reacts with protein carbonyl groups. Our evidence indicates that carno sine can react non-enzymically with protein carbonyl groups, a process term ed 'carnosinylation'. We propose that similar reactions could occur in Cult ured fibroblasts and in vivo. A preliminary experiment suggesting that carn osine is effective in vivo is presented it suppressed diabetes-associated i ncrease in blood pressure in fructose-fed rats, an observation consistent w ith carnosine's anti-glycating actions. We speculate that: (i) carnosine's apparent anti-ageing actions result, partly, from its ability to react with carbonyl groups on glycated/oxidised proteins and other molecules; (ii) th is reaction, termed 'carnosinylation.' inhibits cross-linking of glycoxidis ed proteins to normal macromolecules: and (iii) carnosinylation Could affec t the fate of glycoxidised polypeptides. 2001 Elsevier Science Ireland Ltd. All rights reserved.