Advanced glycation in d-galactose induced mouse aging model

Abstract

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.