Neurochemistry

Normal aging appears to result in significant but restricted neurochemical changes in synapses. Each of the many steps involved in neurotransmission may be altered in some neurons, but it does not appear that there are global changes in the neurochemistry of all synapses. Studies of neurotransmitter synthesis are difficult because most of the synthetic enzymes are unstable and difficult to measure; however, synthesis of ACh has been demonstrated to diminish with age in some brain regions, including the cerebral cortex. Levels of other neurotransmitters (e.g., dopamine) also appear to decline late in life, also in a regionally specific manner. Age-related changes in neurotransmitter receptors have been studied by direct assay of the proteins and by analysis of the binding of labeled neurotransmitters to sections of the brain. Receptors for the neuropeptides and for some amino acid neurotransmitters appear to be relatively resistant to age-related changes. In contrast, ACh, dopamine, and serotonin receptors decline with age in several regions of the brain. Even for synapses at which both neurotransmitter levels and neurotransmitter receptors are maintained, changes in second-messenger systems may produce age-related declines in synaptic function. Such changes may account for an age-dependent loss of plasticity—that is, a decline in the ability of synaptic stimulation to produce the sustained biochemical changes in postsynaptic neurons that underlie learning and memory.