Enhanced 2-deoxy-D-ribose-induced-apoptosis, a phenotype of lymphocytes from old donors, is not observed in the Werner syndrome

Werner syndrome (WS) is an inherited disease characterized by the premature appearance of features of normal aging in young adults. To evaluate the relationship between Werner syndrome and aging, we analyzed the apoptotic response of peripheral blood lymphocytes (PBLs) from two WS patients (mean age 34 years old) incubated with 2-deoxy-D-ribose (dRib), a reducing sugar that induces apoptosis in quiescent cells through an oxidative stress; the results have been compared to two control groups (mean age 35 and 83 years old, respectively). The presence of apoptotic cells was detected by light microscopy, flow cytometry, and agarose gel electrophoresis. In all three groups an increased time-dependent apoptotic response was evident, but the apoptotic response to dRib was lower in WS's cells than in cells from age-matched controls and less than in cells from older subjects. Our results confirm a low susceptibility of WS cells to DNA damaging agents as dRib and suggest that the pathogenic mechanisms underlying normal cellular aging and WS's cellular senescence may be different.