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5 Senescence of Dividing Somatic Cells

Robin Holliday


The senescence of normal diploid cells was first revealed in detailed studies of cultured human fibroblasts (Hayflick and Moorhead 1961; Hayflick 1965). Fibroblasts are connective tissue cells that have a characteristic morphology and synthesize collagen. After a long period of normal growth, the yield of cells per flask began to decrease, and finally reached a very low level, with no further proliferation. These investigators referred to the establishment of a primary culture of normal cells as Phase I, the long period of normal growth as Phase II, and the senescent period as Phase III. Previously, it had been generally assumed that cultured mammalian cells grew indefinitely, but this was based on the growth of neoplastic or transformed cells, and such cell populations are generally known as permanent lines. Saksela and Moorhead (1963) were the first to show that human fibroblasts retain a diploid karyotype during the long period of normal growth, but chromosome abnormalities appear with increasing frequency as cells enter senescence.

There is some controversy about the relationship between senescence, aging, and cell death. If the cells are cultured to a stage where they remain subconfluent, abnormalities in cell morphology are clearly visible. The cells vary in size and shape; the cytoplasm is granular, with many cell inclusions; and debris is formed in the medium. Some of the cells detach to form debris, whereas others remain attached to the substrate. At an earlier stage when the cells still become confluent, these abnormalities are less apparent....

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