Magnetic resonance diffusion tensor imaging (DTI) is a non-invasive in vivo method for characterizing the integrity of anatomical connections and white matter circuitry and provides a quantitative assessment of the brain's white matter microstructure. DTI studies reveal age-related declines in white matter fractional ansiotropy (FA) in normal healthy adults in whom volume declines are not necessarily detectable. The decline is equivalent in men and women, is linear from about age 20 years onwards, and has a frontal distribution. Studies combining regional DTI metrics and tests of specific cognitive and motor functions have shown that age-related declines in white matter integrity are associated with similar declines in interhemispheric transfer, especially dependent on frontal systems. Emerging from recent DTI findings and conceptualizations of neural causes of cognitive decline in aging, we propose three white matter-mediated neural system hypotheses of aging brain structure and function: (1) the anteroposterior gradient, (2) bilateral recruitment of brain systems via the corpus callosum for frontally based task execution, and (3) frontocerebellar synergism. These hypotheses are not mutually exclusive but establish a basis for posing testable questions about brain systems recruited when those used in youth are altered by aging.