Secular trends towards delayed onsets of pathologies and prolonged longevities in Japanese patients with Werner syndrome.

Recent cases of increasingly elderly Werner Syndrome (WS) patients have paralleled increased lifespan in the general population, however, historical temporal lifespan variations in WS have not yet been ascertained. To assess temporal changes in life-span and progeroid comorbidity in WS, all Japanese WS patients documented from 1966-2004 were analyzed for age at onset of diabetes mellitus (DM), malignancy, and death. Of 1,019 WS analyzed, average age significantly increased for all variables studied over the study period. Average age of onset of malignancy and DM in all WS increased from 35.8 to 48.8 years and from 34.9 to 39.7 years, respectively (p < 0.001), while age at death increased from 38.2 to 52.8 years (p < 0.001), vs. 71.7 to 82.7 years (p < 0.001) in the general population. Lifespan increases in WS and the general population suggest a common environmental influence. Unlike the general population, no gender-specific difference in life-span occurred in WS, suggesting a gender-specific differential environmental effect on mutated WRN. Identification of factors responsible for age differences could facilitate improvement in survival and ageing phenotypes of WS patients and the general population.