FIG. 3.

The nigrostriatal dopamine system in aging and PD share important biological features. DA neurodegeneration in PD presents a complex biology of interacting factors. Many of these factors also are present during aging of this system, exhibiting the same direction of change while varying in the magnitude of change. In normal aging, threats to dopamine neuron viability are expressed as impaired function of the system, whereas additional contributions of genetic, environmental, and other unknown factors exaggerate aging-related changes to reach the threshold for dopamine neurodegeneration and symptomatic PD. The multiple shared features of dopamine neuron biology in aging and PD lead to the hypotheses that aging actively creates a pre-PD state and that aging-related changes are the pathological foundation on which the degeneration in PD is built.