Molecular markers of senescence in fibroblast-like cultures.

The loss of replicative capacity in vitro of normal human diploid fibroblasts is a model for studying molecular changes that accompany both regulated growth control and cellular senescence. We describe the molecular phenotype of senescent fibroblasts in terms of markers that are altered with proliferative decline. We describe these markers by analyzing pathways and associated mechanisms related to the responsiveness of proliferatively competent and senescent cells to growth signals including changes in the extracellular environment, growth factors, growth factor receptors, secondary messengers, cell-cycle progression, transcription factors, and the fidelity of DNA synthesis. There is an abundance of molecular markers for senescence in culture at every level of information transfer. Although it seems clear that some alterations in gene expression with senescence are the result of specific changes in upstream events, more global dysregulation of coordinated growth control point to as yet undefined mechanisms.