Figure 1. Developmental origins of premature and normal aging. Individuals with WRN are endowed with specific epigenetic changes in several hundred genes (indicated by red dots) before the disease manifests. This is consistent with a multifactorial model of aging, in which the WRN-specific epigenetic burden, one that may arise early in development, is associated with a lowered threshold and increased risk for age-related diseases. In order to be affected, the number of adverse factors including epigenetic changes (red dots) in an individual must exceed a certain threshold.