Advanced glycation in D-galactose induced mouse aging model

It was first reported in China that injection of a low dose of D-galactose into mice could induce changes which resembled accelerated aging. The aging model shows neurological impairment, decreased activity of anti-oxidant enzymes, and poor immune responses. However, the underlining mechanism remains largely unknown. D-galactose is a reducing sugar that can form advanced glycation endproducts (AGE) in vivo. To investigate the role of AGE in this aging model, a group of 5-month-old C57 mice were injected daily with D-galactose, D-galactose modified AGE-lysine (AGE-lysine), L-glucose, L-lysine, or control buffer for 8 weeks. Two additional groups were treated with the AGE formation inhibitor, aminoguanidine. The results show that D-galactose, L-glucose, and AGE-lysine treated mice had a significant increase in serum AGE levels, memory latency time and error rate, and skin hydroxyproline content. Similar to aged controls, these mice also had a significant decrease in motor activity, lymphocyte mitogenesis, interleukin-2 (IL-2) production, and superoxide dismutase (SOD) enzyme activity. The aminoguanidine treated D-galactose-injected mice, however, showed no significant changes in these parameters in comparison with young controls. These data indicate that D-galactose and L-glucose form AGEs in vivo and that elevated AGEs may accelerate the aging process. The fact that both D-galactose and AGE treated mice resemble aged mice suggests that advanced glycation, at least partially, accounts for the mechanism of this aging model. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.