DETERIORATING COLLAGEN-SYNTHESIS AND CELL ULTRASTRUCTURE ACCOMPANYING SENESCENCE OF HUMAN NORMAL AND WERNERS SYNDROME FIBROBLAST CELL STRAINS

Ultrastructural changes that accompanied senescence, in vitro, of 6 normal fibroblast cell strains corresponded to the morphological characteristics of a Werner''s syndrome progeroid cell strain: greatly increased size of midnuclear diameters; heavy vacuolation; maturation of predominantly primary to secondary lysosomes; increase in multilobed nuclei; dilation of mitochondrial cristae; dilation of rough endoplasmic reticulum and the filling of intermembrane space with electron-dense particles [presumably protein]; and vacuolar accumulation of fibrous material which was later discharged into the medium. This fibrous material was produced only by late-passage fibroblasts and Werner''s syndrome fibroblasts and had an ultrastructure dissimilar from that of normal collagen fibers produced by exponentially-growing cultures. The fibrous debris had a high subunit MW [approximately 200,000 daltons], an amino acid composition that included hydroxyproline, hydroxylsine and relatively large amounts of proline and glycine, and was degraded by collagenase. This protein may be a form of procollagen produced by either incorrect maturation of mRNA or incomplete processing of procollagen.