Prevention of diabetes-increased aging effect on rat collagen-linked fluorescence by aminoguanidine and rutin.

Products from the advanced Maillard reaction, which increase during aging and diabetes, may contribute to the development of the typical pathology of aging and diabetes. These compounds are detectable only by their characteristic fluorescence, and few data based on long-term studies are available. For this reason, we studied subcutaneous skin collagen fluorescence in 57 nondiabetic (10- to 110-wk-old) and 74 streptozocin-induced diabetic (10- to 22-wk-old) rats. An exponential increase (r = 0.969, P less than 0.001) of collagen-linked fluorescence (excitation at 370 nm, emission at 440 nm) was observed with aging; after a lag, diabetes induced an earlier dramatic elevation of the fluorescence, suggesting a more complicated phenomenon than simple accumulation. To prevent such increases, the effects of 1 g.kg-1.day-1 aminoguanidine, suggested to be an inhibitor of the advanced glycosylation reaction, and 1 g.kg-1.day-1 rutin, an aldose reductase inhibitor, in drinking water were tested. Both treatments had a significant lowering effect on collagen fluorescence in diabetic rats. The mechanisms by which aminoguanidine and rutin prevent the accumulation of fluorescence are unknown, but these observations raise the question of whether they could be identical. If fluorescence is a marker for age-related pathologies and diabetic sequelae, aminoguanidine and rutin could have therapeutic effects in their prevention.

Age-related increase of collagen fluorescence in human subcutaneous tissue.

Nonenzymatic glycation produces compounds with characteristic fluorescence in long-lived proteins. We recently described the influence of age in rat collagen-linked fluorescence. To examine the effect of age in humans, we studied the subcutaneous collagen-linked fluorescence in samples from 26 subjects of both sexes (age range, 42 to 78 years) who were undergoing vascular surgery. Intensity of fluorescence at 385 nm (upon excitation at 335 nm) and 440 nm (upon excitation at 370 nm) increased exponentially with age (r = .827, y = 114 + e0.038x, P less than .001; and r = .905, y = 36 + e0.039x, P less than 0.001, respectively). The two sets of data exhibited a high degree of correlation (r = .980, P less than .001, n = 26). Age-adjusted fluorescence data did not correlate with sex, body weight, or type of vascular pathology. The collagen fluorescence accumulation rate was 3.7% per year, and the characteristic time (CT) was 26 to 27 years. We conclude that the fluorescence measurement is a reliable methodology that can be used as a marker for biological age until new, more-specific tools are available.

Correlation of collagen-linked fluorescence and tendon fiber breaking time.

We review in this paper some reported data on age-dependent modification of proteins pointing out the relationship between the increase of nonenzymatic glycation in abdominal skin collagen of Wistar rats, evaluated by fluorescence intensity, and tendon breaking time, used as a parameter of collagen stiffness. Fluorescence intensity data linearly correlate with the breaking times of collagen fibers from Wistar rats reported from different sources, according to the hypothesis of a common etiological mechanism. It is possible to suppose that posttranslational modifications of proteins play a role in the tissue aging and their level in collagen may be used as a parameter for quantitation.