FAILURE OF SENESCENT HUMAN FIBROBLASTS TO EXPRESS THE INSULIN-LIKE GROWTH FACTOR-I GENE

Senescent human diploid fibroblasts express several growth-regulated genes but fail to express others. In this paper we show, by a very sensitive technique (reverse transcriptase-polymerase chain reaction), that senescent cells fail to express insulin-like growth factor-1 (IGF-1) mRNA, which is expressed in moderate amounts by young cells. Human fibroblasts immortalized by transfection with a temperature-sensitive SV40 T antigen gene regain the ability to express IGF-1 mRNA, but only at the permissive temperature of 34-degrees-C. Under these conditions, the immortalized human fibroblasts grow even in 1% serum. At the restrictive temperature of 39-degrees-C, the temperature-sensitive T antigen is nonfunctional, IGF-1 RNA is not detectable, and the cells fail to grow even in 10% serum. The failure to express IGF-1 mRNA in postsenescent cells can be ascribed, at least in part, to a transcriptional mechanism. Despite the correlation among immortalization by SV40 T antigen, expression of IGF-1, and growth, it seems unlikely that the failure to express IGF-1 is the sole cause of cellular senescence; other requirements must be postulated.