A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice
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We developed a complex dietary supplement designed to offset five key mechanisms of aging and tested its effectiveness in ameliorating age-related cognitive decline using a visually cued Morris water maze test. All younger mice (<1 year old) learned the task well. However, older untreated mice (>1 year) were unable to learn the maze even after 5 days, indicative of strong cognitive decline at older ages. In contrast, no cognitive decline was evident in older supplemented mice, even when ∼2 years old. Supplemented older mice were nearly 50% better at locating the platform than age-matched controls. Brain weights of supplemented mice were significantly greater than controls, even at younger ages. Reversal of cognitive decline in activity of complexes III and IV by supplementation was significantly associated with cognitive improvement, implicating energy supply as one possible mechanism. These results represent proof of principle that complex dietary supplements can provide powerful benefits for cognitive function and brain aging.
KeywordsCognitive aging Learning Aging Dietary supplements Mitochondria Brain mass
This research was supported by a grant to CDR from the Natural Sciences and Engineering Research Council of Canada. We thank Zoya Tov for her contributions to diet preparation and technical support for the experiments.
- Aksenov V, Long J, Lokuge S, Foster JA, Liu J, Rollo CD (2010) A dietary supplement ameliorates locomotor, neurotransmitter and mitochondrial aging. Exp Biol Med 335:66–76Google Scholar
- Carney JM, Starke-Reed PE, Oliver CN, Landum RW, Cheng MS, Wu JF, Floyd RA (1991) Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-α-phenylnitrone. PNAS 88:3633–3636PubMedCrossRefGoogle Scholar
- Herman BH, Nagy ZM (1977) Development of learning and memory in mice genetically selected for differences in brain weight. Dev Psychol 10:65–75Google Scholar
- Kausler DH (1994) Learning and memory in normal aging. Academic, San DiegoGoogle Scholar
- Lemon JA, Boreham DR, Rollo CD (2003) A dietary supplement abolishes age-related cognitive decline in transgenic mice expressing elevated free radical processes. Exp Biol Med 228:800–810Google Scholar
- Lemon JA, Boreham DR, Rollo CD (2005) A complex dietary supplement extends longevity of mice. J Gerontol 60A:275–279Google Scholar
- Osendarp SJ, the NEMO Study Group (2007) Effect of a 12-mo micronutrient intervention on learning and memory in well-nourished and marginally nourished school-aged children: 2 parallel, randomized, placebo-controlled studies in Australia and Indonesia. Am J Clin Nutr 86:1082–1093PubMedGoogle Scholar
- Rollo CD, Ko CV, Tyerman JGA, Kajiura L (1999) The growth hormone axis and cognition: empirical results and integrated theory derived from giant transgenic mice. Can J Zool 77:1874–1890Google Scholar
- Wehner JM, Silva A (1996) Importance of strain differences in evaluations of learning and memory processes in null mutants. MRDD Res Rev 2:243–248Google Scholar
- Widmann CN, Beinhoff U, Riepe MW (2011) Everyday memory deficits in very mild Alzheimer’s disease. Neurobiol Aging. doi: 10.1016/j.neurobiolaging2010.03.012