CHANGES IN JUN N-TERMINAL KINASE ACTIVATION BY STRESS DURING AGING OFCULTURED NORMAL HUMAN FIBROBLASTS

The molecular changes associated with the aging process include the re duced activity of transcription factors (such as AP-1) and an impaired response to stress, which has been well documented in the case of the heat-shock (HS) response. Using human diploid fibroblasts of early an d late passages as an in vitro model for aging, we elucidated changes in the activation of jun N-terminal kinases (JNKs), which play an impo rtant role in the mammalian stress response. We Sound that early-passa ge cells exhibited a greater degree of JNK activation in response to H S and ultraviolet (UV) C light treatments than did late-passage cells. Decreased JNK activation was dependent on the number of passages but was not affected by varying doses of UV irradiation. Analysis of prote in kinase A, mitogen-activated protein kinase, and src-related tyrosin e kinases revealed no decreased activities in aged cells, indicating a selective rather than generalized decrease in kinase activities durin g aging. A further understanding of this impaired activation of JNK ma y provide insights into the mechanisms of stress response and cellular aging. (C) 1996 Wiley-Liss, Inc.