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

Abstract

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.

A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice

“…This, combined with our earlier results with transgenic growth hormone mice (that express neuropathology similar to AD) (Lemon et al 2003), suggests promise for amelioration of human neuropathologies.…”

“…Breeding and husbandry of mice (random bred C57BL/ 6J_SJL) were previously described (Lemon et al 2003). Protocols adhered to the Canada Council on Animal Care.…”

“…Daily dosages were derived from recommended human values adjusted for body size and the higher metabolic rate of mice. Supplemented mice received 1 dose/day of DSP that was soaked onto small pieces of bagel in their home cages (details in Lemon et al 2003;Aksenov et al 2010). All mice avidly ate the supplement confirming no issues concerning palatability.…”

“…We developed a complex dietary supplement (DSP) designed to target five key mechanisms of aging (oxidative stress, inflammation, mitochondrial function, insulin resistance, and membrane integrity) ( Table 1). The DSP markedly improved learning in a model of accelerated cognitive aging (transgenic growth hormone mice) (Lemon et al 2003) and extended longevity of normal mice by 11% (Lemon et al 2005). It entirely prevented age-related declines in spontaneous motor activity and elevated brain mitochondrial function (complex III) in old age while reducing the rate of free radical generation.…”

“…Additionally, the DSP protected mice from oxidative damage associated with aging and radiation (Lemon et al 2008a, b;Aksenov et al 2010). Previous cognitive benefits of the DSP were demonstrated in transgenic growth hormone mice that express accelerated aging and rapid cognitive decline (Lemon et al 2003). Here we demonstrate equally striking preservation of cognitive functions in aging normal mice using the MWM.…”