INFLUENCE OF AGE AND LONG-TERM DIETARY RESTRICTION ON ENZYMATICALLY MEDIATED CROSS-LINKS AND NONENZYMATIC GLYCATION OF COLLAGEN IN MICE

This study was designed to investigate the effects of lifetime diet re striction on collagen crosslinking in skin, tail tendon, aorta, and lu ng in mice. Difunctional enzymatic crosslinks decreased with age in al l 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 gl ycation product, in aorta. There was no change in glucitolyllysine con tent with age. Difunctional crosslinks, glucitolyllysine, and collagen -associated fluorescence were decreased in diet-restricted animals rel ative to ad libitum fed animals in some tissues at some time points; h owever, correlations were not observed among these different effects, or between different tissues. Diet restriction did not affect nonreduc ible ''mature'' crosslinks. These studies suggest that: (1) lifetime d iet restriction is associated with decreased collagen-associated fluor escence, suggestive of advanced glycation products, in older animals; (2) age-related increases in collagen stiffening and its decrease by d ietary restriction cannot be explained solely by alterations in lysyl oxidase-mediated crosslinking, the levels of which are tissue dependen t; (3) lysyl oxidase-mediated crosslinking and nonenzymatic glycation of collagen are independently influenced by dietary restriction and ag ing.