Carnosine reacts with protein carbonyl groups: another possible role for the anti-ageing peptide?

Carnosine (beta -alanyl-L-histidine) can delay senescence and provoke cellu lar rejuvenation in cultured human fibroblasts. The mechanisms by which suc h a simple molecule induces these effects is not blown despite carnosine's well documented anti-oxidant and oxygen free-radical scavenging activities. Carbonyl groups are generated on proteins post-synthetically by the action of reactive oxygen species and glycating agents and their accumulation is a major biochemical manifestation of ageing. We suggest that, in addition t o the prophylactic actions of carnosine, it may also directly participate i n the inactivation/disposal of aged proteins possibly by direct reaction wi th the carbonyl groups on proteins. The possible fates of these 'carnosinyl ated' proteins including the formation of inert lipofuscin, proteolysis via the proteasome system and exocytosis following interaction with receptors are also discussed. The proposal may point to a hitherto unrecognised mecha nism by which cells/organisms normally defend themselves against protein ca rbonyls.