Aging, hypoxia, and thiamin deficiency diminish motor performance. Similar alterations of ACh, DA, and glutamate metabolism accompany hypoxia, thiamin deficiency, and aging. Both aging and hypoxia reduce ACh release and stimulate DA and glutamate release. Presynaptic enhancement of DA and glutamate release may be important in the production of cell damage that may contribute, in part, to age-related deficits in motor as well as cognitive function. The decline in ACh release may be important in the production of the cognitive deficits. An understanding of the interactions of neurotransmitters in hypoxia and thiamin deficiency aids our understanding of normal aging and increases the possibility of developing better treatments for the multiple neurotransmitter deficiencies that accompany many metabolic, age-related, and chronic degenerative disorders.