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ORIGINAL RESEARCH ARTICLE

A Dietary Supplement Abolishes Age-Related Cognitive Decline in Transgenic Mice Expressing Elevated Free Radical Processes

J.A. Lemon^*, D.R. Boreham and C.D. Rollo^*,1

^* Departments of Biology and
Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton Ontario, Canada L8S 4K1

We previously found that transgenic mice overexpressing growth hormone (TGM) have elevated and progressively increasing free radical processes in brain that strongly correlates with reduced survivorship. Young mature TGM, however, displayed vastly enhanced learning of an eight-choice cued maze and qualitatively different learning curves than normal controls. Here we document the age-related patterns in learning ability of TGM and normal mice. Learning appeared inferior in both genotypes of very young mice but TGM were confirmed to be superior to normal mice upon maturity. Older TGM, however, showed rapid age-related loss of their exceptional learning, whereas normal mice at 1 year of age showed little change. The cognitive decline of TGM was abolished by a complex "anti-aging" dietary supplement formulated to promote membrane and mitochondrial integrity, increase insulin sensitivity, reduce reactive oxygen and nitrogen species, and ameliorate inflammation. Results are discussed in the context of reactive oxygen and nitrogen species, long-term potentiation, learning, aging and neuropathology, based on known impacts of the growth hormone axis on the brain, and characteristics of TGM.

Key Words: aging • reactive oxygen and nitrogen species • learning • memory • long-term potentiation • neuronal signal transduction • transgenic growth hormone mice • growth hormone • insulin-like growth factor • cognitive decline

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