Influence of age and long-term dietary restriction on enzymatically mediated crosslinks and nonenzymatic glycation of collagen in mice.

This study was designed to investigate the effects of lifetime diet restriction on collagen crosslinking in skin, tail tendon, aorta, and lung in mice. Difunctional enzymatic crosslinks decreased with age in all tissues except skin, while mature crosslinks showed almost no change with age. Collagen-associated fluorescence, assayed in skin and tail tendon, increased with age, as did pentosidine, a specific advanced glycation product, in aorta. There was no change in glucitolyllysine content with age. Difunctional crosslinks, glucitolyllysine, and collagen-associated fluorescence were decreased in diet-restricted animals relative to ad libitum fed animals in some tissues at some time points; however, correlations were not observed among these different effects, or between different tissues. Diet restriction did not affect nonreducible "mature" crosslinks. These studies suggest that: (1) lifetime diet restriction is associated with decreased collagen-associated fluorescence, suggestive of advanced glycation products, in older animals; (2) age-related increases in collagen stiffening and its decrease by dietary restriction cannot be explained solely by alterations in lysyl oxidase-mediated crosslinking, the levels of which are tissue dependent; (3) lysyl oxidase-mediated crosslinking and nonenzymatic glycation of collagen are independently influenced by dietary restriction and aging.