Aim: 

To evaluate both amount of protein oxidative modifications (quantitative approach) and targets of those free-radical mediated lesions (qualitative approach) in several age-related diseases, assuming oxidative stress as a causal factor in ageing.

Methods: 

Samples, ranging from cell culture to human subjects, were analyzed in different pathological contexts. For quantitative measurement of oxidative damage, a gas-chromatography mass-spectrometric approach was taken for structurally characterized markers of oxidative damage. For qualitative assessment of oxidative targets, western blot after 2D electrophoresis was used, with MALDI peptide fingerprinting.

Results: 

Quantitatively, increases in oxidative damage were evidenced in samples such as aorta, kidney and plasma from diabetes models, supporting the relevance of glycoxidative pathways (i.e. advanced glycation endproduct formation). In addition, neurodegenerative diseases also show increased oxidative damage, with disease and location-specific patterns. Specifically, lipoxidative reactions seem commonly in those diseases. Qualitatively, no specific pattern could be described. Different proteins, ranging from mitochondrial enzymes up to cytoskeletal components, were modified by oxidative stress. Strikingly, several growth factors and growth factor receptors were modified by glycoxidative products both in diabetes and in neurodegenerative diseases. This may constitute a novel pathogenic pathway.

Conclusions: 

Both quantitative and qualitative, disease-specific oxidation patterns are evident in age-related diseases. The lack of common targets reveal heterogeneity of the implication of oxidative stress in age-related diseases, despite modification of growth factor-receptors and growth factors itself could participate as a novel pathogenic event.