Cellular Aging: Cell Death

First identified in the late 1960s by Leonard Hayflick and his collaborators, the term cellular senescence refers to the fact that normal, nonmalignant cells of vertebrates do not divide indefinitely in culture, but in time terminally differentiate and enter a prolonged postmitotic phase, eventually dying in the culture dish. Because the number of divisions that the cells can undergo is inversely related to the age at which they were explanted, cellular senescence has been associated with aging—though there is little evidence that, except in limited situations, individuals at the ends of their lives have "run out of cells." The mechanism for cell senescence is not completely understood. One explanation for the limitation in cell replication is based on the importance of the end-piece, or telomere, of a chromosome. The manner in which DNA is Scanning electron micrograph (SEM) image showing the death of a cell (apoptosis). (Phototake photo by Gopal Murti.) replicated results in the loss of a small portion of DNA (an Okazaki fragment) from the end of the chromosome with each replication. This problem is addressed by the addition to the end of the DNA, during early embryonic life, of a stretch of meaningless, noncoding DNA called a telomere. Thus, at each division a piece of this expendable DNA is shed. Under culture conditions, or in conditions of excessive proliferation, such as chronic challenge to the immune system, the cells eventually use up their telomeres and cease proliferation. Cancerous cells reacquire the embryonic ability to reconstruct the telomere, and thus become immortal.