Genetic effects on the longevity of cultured human fibroblasts. I. Werner's syndrome.

Fibroblast cultures were established from skin biopsies from 4 male Werner's syndrome patients, aged 45-50. Several subcultures were obtained from each primary outgrowth and these were passaged to the end of their in vitro lifespan. Their average longevity was significantly less than control skin fibroblasts, but there was extreme variability amongst parallel cultures. In the most thoroughly studied case, the longevity of 19 subcultures derived from a single biopsy varied from 5 to 26 passages, showing that there was considerable heterogeneity in the growth potential of the cells in the primary culture. Moreover, the growth rate from any one culture was not uniform, since long periods of slow growth were sometimes succeeded by much more rapid proliferation. These features of Werner's syndrome fibroblast populations are not seen in cultures from normal individuals. The longevity of fibroblasts from one progeria patient was also shown to be much shorter than controls. Metaphases from 3 Werner's patients demonstrated a much higher frequency of chromosome abnormalities than in normal fibroblasts and also provided evidence of subclones containing a characteristic 'marker' chromosome.