Protein nonenzymatic modifications and proteasome activity in skeletal muscle from the short-lived rat and long-lived pigeon

What are the mechanisms determining the rate of animal aging? Of the two major classes of endothermic animals, bird species are strikingly long-lived compared to similar size mammalian counterparts. Since oxidative stress is causally related to the basic aging process, markers of different kinds of oxidative damage to proteins (glutamic semialdehyde, aminoadipic semialdehyde, N-epsilon-(carboxyethyl)lysine; N-epsilon-(carboxymethyl)lysine, N-epsilon-(malondialdehyde)lysine and dinitrophenylhydrazyne-reactive protein carbonyls), peptidase activities of the proteasome. and amino acid and membrane fatty acyl composition were identified and measured in skeletal muscle from the short-lived rat (maximum life span, 4 years) and compared with the Iona-lived pigeon (maximum life span, 35 years). Skeletal muscle from pigeon showed significantly higher levels of glutamic semialdehyde, protein carbonyls (by western blot), N-epsilon-(carboxyethyl)lysine and N-epsilon-(carboxymethyl)lysine. No differences were observed for aminoadipic semialdehyde, whereas the lipoxidation marker N-epsilon-(malondialdehyde)lysine displayed a significant low steady-state level, probably related with their significantly lower membrane unsaturation. The amino acid compositional analysis revealed that arginine, serine, threonine and methionine showed significantly lower levels in pigeon. Finally, pigeon samples showed also significantly lower levels of the peptidase activities of the proteasome. These results reinforces the role of structural components such as membrane unsaturation and protein composition in determining the longer maximum life span showed by birds compared with mammals of similar body size. (C) 2004 Elsevier Inc. All rights reserved.