Fibroblast Cells Physiological Changes

Fibroblasts were among the first cell type to be propagated in culture, largely because they grow so readily out of most tissue explants. Standard tissue-culture conditions, particularly the use of serum (which contains platelet factors), resemble a wounded environment, and favor the growth of fibroblasts. It is therefore principally for historic reasons that fibroblasts, as opposed to other cell types, have been most extensively used to study cellular aging—or, more accurately, cellular senescence—in culture.

In the early 1960s, Leonard Hayflick and colleagues carefully documented the fact that normal human fibroblasts do not divide indefinitely in culture. Working with human fetal tissues, Hayflick showed that fibroblasts that grew out of tissue explants initially proliferated well, with population doubling times of about twenty-four hours. He then allowed the cells to completely cover the culture dish (grow to confluence) before dispersing and reseeding them at low density. This process is called passaging the cells. With each passage, the cultures gradually accumulated nondividing cells. After fifty or so doublings, the cultures consisted entirely of nondividing fibroblasts. This phenomenon was termed the finite, or limited, replicative life span of cells. Hayflick was the first to connect this loss of proliferative potential with aging, and termed the process that limits cell division cellular aging. It has also, and perhaps more accurately, been termed replicative senescence.

Since the 1960s, many cell types from many vertebrate species have been shown to have a limited replicative life span. Many of these studies have used cells in culture, but several have followed cells in vivo or cells serially transplanted into animals. Nonetheless, much of our knowledge about the causes and consequences of replicative senescence comes from studies of human fibroblasts in culture.