Aging is part of the natural progression of life accompanied by an undesired decline in brain
functions such as learning and memory. The mechanisms underlying the deterioration are
poorly understood, hindering early diagnosis and intervention. While the brain is only 2% of the
total body weight, it comprises 20% of the body’s energy consumption. This study explored the
efficiency of an aged brain's energy metabolism, aiming to decipher the metabolic mechanisms
related to diminishing brain functionality during aging. The brain area for memory and learning,
the hippocampi, of both young and aged mice were dissected, and metabolites were measured
using metabolomics analysis, a high throughput method to detect hundreds of metabolites at
once. 593 metabolites were detected. The changes in glucose metabolism, a major part of
energy consumption, were examined. Glucose concentration in the aged hippocampus
increased dramatically during hippocampal context exploration, compared to a very mild
increase in young mice. A significant increase in the levels of ketone bodies, another energy
source, was also observed in aged mice during brain activity. Analyzing the steps of the TCA
cycle, which produces ATPs with these energy compounds, varying levels of metabolites were
discovered between young and aged mice; however, they showed no consistent change.
Altogether, by utilizing metabolomics analysis, the reduction in energy consumption efficiency
during brain activity compared to the young brain was pronounced. These findings may help
guide future studies of disease progression and the development of therapeutic targets for the
symptomatic treatment of declining brain function during aging.