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.
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Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
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D000375:Aging; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005690:Galactose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000097:blood*; D006146:Guanidines / Q000494:pharmacology; D006909:Hydroxyproline / Q000187:drug effects / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood; D007858:Learning / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood / Q000187:drug effects
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007376:Interleukin-2; D013482:Superoxide Dismutase; D005947:Glucose; D008239:Lysine; D006909:Hydroxyproline; C004479:pimagedine; D005690:Galactose