Collagen Racemization and Deposition in the Lungs of Aged Rats

Isomerization of amino acids in proteins has recently been identified as a part of the aging process. Increases in D-amino acids as a consequence of isomerization influence the function and structure of proteins. Senescence-related pulmonary diseases, such as chronic obstructive pulmonary disease, are thought to be caused by reductions of lung function with age. We hypothesized that changes of protein structure in lung tissue induced by the isomerization of amino acids could result in decreased lung function. Therefore, we examined whether isomerization of amino acids takes place in the lungs of rats as they age. We measured the content of L- and D-amino acids in collagen 1 by HPLC using a chiral column. We found that collagen 1 was increasingly racemized with age, so that significantly higher proportions of D-Ser were present in 12- and 24-month-old rats than in 8-week-old rats. D-Asp increased slightly but not significantly. We also investigated the localization of collagen 1 in lung tissue. Stacks of collagen 1 were observed in the parenchyma and airway wall, and age-dependent changes were especially prominent in the airway wall. Racemization of collagen 1 could therefore influence lung function and contribute to pulmonary diseases.