Is increased arachidonic acid release a cause or a consequence of replicative senescence?

Arachidonic acid (AA) has been related to both stimulation and inhibition o f cellular proliferation. During replicative senescence of human fibroblast s, increased levels of AA have been thought to play a causal role in the li mited proliferative capacity of the cells. To clarify the role of AA in the proliferation of normal fibroblasts and in cellular senescence, we examine d uptake from and release of AA into the culture media and its effects on D NA synthesis. Our results indicate that some aspects of AA metabolism in no rmal human fibroblasts aged in culture an significantly different in compar ison to early passage cells. Particularly, AA release following different m itogenic stimulation is higher in senescent than in young cells. Notwithsta nding this significant difference, AA, at the concentration used, has no in hibitory effect on fibroblast DNA synthesis. Moreover AA and prostaglandins are responsible for the proliferative block in neither senescent cells nor mediate ceramide inhibition of DNA synthesis. So our results suggest that the increasing AA release is not causal, but rather the result of in vitro aging. (C) 2001 Elsevier Science Inc. All rights reserved.