ACCELERATED LOSS OF TELOMERIC REPEATS MAY NOT EXPLAIN ACCELERATED REPLICATIVE DECLINE OF WERNER SYNDROME CELLS

The Werner syndrome (WS) is characterized by the premature onset and a ccelerated rate of development of major geriatric disorders, including atherosclerosis, diabetes mellitus, osteoporosis, ocular cataracts, a nd various neoplasms. Cultures of WS skin-fibroblastlike cells have be en previously shown to undergo accelerated rates of decline of their r eplicative potentials and to exhibit variegated chromosomal translocat ions and deletions. Since the replicative decline of normal somatic ce lls is associated with a loss of telomeric repeats, we investigated th e kinetics of telomeric repeat loss in WS cells. The mean length of te lomere restriction fragments (TRF) from the earliest passages of WS ce lls studied was not shorter than those of controls, possibly reflectin g selective pressure for subsets of cells with relatively high residua l replicative capacity. Statistical evidence indicated an accelerated shortening of TRF length in serially passaged WS cultures, but the mea n TRF lengths of WS cultures that had ceased replicating were signific antly longer than those of senescent controls. Thus, while accelerated loss of telomeric repeats could potentially explain the rapid decline in proliferation of WS cells, it is possible that WS cells exit the c ell cycle via mechanisms that differ from those of replicatively senes cent cells from control subjects.