Advanced glycation in D-galactose induced mouse aging model

Mech Ageing Dev. 1999 May 17;108(3):239-51. doi: 10.1016/s0047-6374(99)00022-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Avoidance Learning / drug effects
  • Cell Division / drug effects
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Erythrocytes / drug effects
  • Erythrocytes / enzymology
  • Female
  • Galactose / pharmacology*
  • Glucose / pharmacology
  • Glycation End Products, Advanced / blood*
  • Guanidines / pharmacology
  • Hydroxyproline / drug effects
  • Hydroxyproline / metabolism
  • Interleukin-2 / blood
  • Learning / drug effects
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lysine / analogs & derivatives
  • Lysine / pharmacology
  • Memory / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Nervous System Diseases / blood
  • Nervous System Diseases / chemically induced
  • Nervous System Diseases / physiopathology
  • Skin / drug effects
  • Skin / metabolism
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / drug effects


  • Enzyme Inhibitors
  • Glycation End Products, Advanced
  • Guanidines
  • Interleukin-2
  • Superoxide Dismutase
  • Glucose
  • Lysine
  • Hydroxyproline
  • pimagedine
  • Galactose