Brain glucose and energy metabolism during normal aging

Abstract

The mature, healthy, non-starved mammalian brain uses glucose only as a source of energy in the form of ATP, which is necessary for several metabolic processes, such as the maintenance of cellular homeostasis via ion homeostasis, maintenance of the integrity of cellular compartments, and intracellular transportation processes for the formation of several neurotransmitters, neurotransmission itself and a few anabolic reactions. Glucose breakdown contributes to the formation of the neurotransmitters: acetylcholine, glutamate, aspartate, gamma-aminobutyrate, and glycine. Normal cerebral aging is associated with an incipient perturbation in both cerebral glucose and related metabolism, that determines an energy deficit and thus an imbalance in cell homeostasis after the 7th or 8th decade of human life, indicating a threshold phenomenon. This is evidenced by morphological/morphobiological abnormalities comprising neuronal loss and structural changes. These events are thought to cause a marked reduction in the biological plasticity of the brain, which may be severely involved after additional stress situations such as ischemia, hypoxia or hypoglycemia. The age-related increasing perturbation of neuronal homeostasis may represent a stress situation capable of inducing heat shock proteins effecting gene activity. Thus, several age-related metabolic abnormalities at the cellular level, starting with a deficient neuronal glucose and energy metabolism, can be regarded as risk factors for neuronal damage and death, and hence reduced mental capacity.