Different Kinetics of Senescence in Human Fibroblasts and Peritoneal Mesothelial Cells

Abstract

Senescence has been reported for a wide variety of human cell types. In cultures of human fibroblasts the process is due to a percentage of the cells becoming senescent at each passage rather than all the cells entering senescence simultaneously at the end of the life span. By measuring the percentage of fibroblasts which are still cycling at each passage, a rate of decline in the growth fraction, which mirrors the rate of senescence, can be obtained. However, such an analysis has never been undertaken in multiple cell types using the same method to identify cycling cells. It is thus unknown if the rate of senescence is the same or different in cultures of different human cell types. To answer this question the rates of decline in the cycling fractions were simultaneously measured in two cultures of human cells (AGO7086A, peritoneal mesothelial cells; and 2DD, human dermal fibroblasts) which have practically identicalin vitrolife spans. 2DD fibroblasts showed a rate of decline of 0.89% cycling cells per population doubling when the data obtained were fitted to a simple linear equation. However, AGO7086A gave a decline of approximately 2.2% per population doubling. Thus mesothelial cells enter senescence significantly faster than fibroblasts (P< 0.001). This decline in the growth fraction was accompanied by an increasing fraction of mesothelial cells which retained detectable endogenous β-galactosidase activity at pH 6. Such activity has previously been shown to be associated with senescent human fibroblasts. These findings suggest that the process of senescence has common features in different cell lineages but that the rate of the process can differ markedly between them.