Several changes in the functional characteristics of fibronectin (FN) have been noted as cells become senescent in culture. In a previous report we showed that the steady state level of FN mRNA increases significantly during the process of in vitro cellular aging in a fibroblast strain. Because a phenomenon observed in one cell strain may not be the case in other cell strains, we extended the previous study and confirmed that this is a common phenomenon in at least two fibroblast strains of different origin. The greatest change in the proportion of cells expressing high levels of FN occurs near the end of a culture's proliferative potential. The proportion of cells unable to synthesize DNA follows a similar pattern. We also found that increasing cell size correlates closely with higher levels of FN expression. Thus, there is a clear correlation between increased FN mRNA content and in vitro cellular senescence. In order to see if this phenomenon could also be observed in cells aged in vivo, we analyzed cells aged in vivo. We found that fibroblasts from donors of higher age show lower labeling index, express a higher level of FN and come to have a larger cell area, similar to cells aged in vitro. This strongly suggests that a fibroblast in vivo ages with aging of the individual in like manner to that observed in in vitro aging cells, that is, by exhausting division potential. This supports studies using in vitro aging cells as a model for cellular aging in vivo.

This work was supported in part by grants-in-aid from Ministry of Education, Science and Culture of Japan ( # 02771747 and # 04836018).