Age effects on the signal characteristics of white matter (WM) were examined via magnetic resonance imaging (MRI). Global and local patterns of WM degeneration were demonstrated using a new image analysis methodology. Significant cross-sectional and longitudinal age effects were found in the WM, primarily in the left hemisphere. Importantly, signal changes, which likely reflect WM demyelination, and changes in water, protein and mineral content of tissue, were unrelated to volumetric changes. Thus, measures of tissue characteristics provide unique and complementary information to widely used measures of brain atrophy. Moreover, signal measurements displayed stronger associations with age and can potentially be more sensitive than volumetric measures as indicators of preclinical disease, because they reflect changes in the underlying tissue composition. To our knowledge, our study is the first documentation of longitudinal age- and region-dependent changes in magnetic resonance signal characteristics of WM fibers, reflecting underlying degenerative effects of aging.