Cellular Aging: Basic Phenomena

Development proceeds through many steps that ultimately produce germ (reproductive cells) and somatic (nonreproductive) cell lineages. The germ cell lineage population is potentially immortal, because the genes it carries can be passed on indefinitely. The somatic cells will ultimately age and die. Early studies by Carrel and coworkers suggested that, when isolated from organisms, individual somatic cells were immortal. This view remained prominent for many years, though subsequent studies showed that it was actually untrue.

Figure 1 Some internal structures found in a normal human cell. The cell depicted in this figure remains in the body and therefore exhibits no effects of senescence. SOURCE: Author and GGS Inc.

Figure 2 Stages of cell cycle and various stages of mitosis. Also depicted are senescence (G_senescent ) and the escape from senescence to immortality that can occur after treatment with the SC-40 virus. SOURCE: Author

Studies conducted in many laboratories have shown that after the migration of cells from tissue pieces into culture vessels there is a phase of rapid proliferation, followed by one of declining proliferative capacity, and ultimately a total loss of mitotic activity. Cultures that have entered this permanently quiescent state are termed "senescent." During this later nonmitotic phase, the cells change in size and morphology, become granular in appearance, and accumulate debris. The loss of proliferative capacity in human diploid cell culture populations is a well-regulated phenomenon. As populations of cells divide successive times, the generation time of the culture increases, and there is also failure of an increasing fraction of the population to replicate at all. There is strong evidence that substantial heterogeneity develops in populations of cells as they proliferate, with some members of the population exhibiting a high proliferative capacity while others are capable of only a small number of divisions.

Cellular senescence has been observed in a variety of cell types. Although the proliferative capacity differs between various types of cells, for any given cell type the proliferative capacity tends to be relatively constant. The inability of cell cultures to proliferate indefinitely is neither the result of technical difficulties nor of the depletion of essential metabolites. Hayflick and Moorhead (1961) concluded that the limited lifespan phenomenon observed in human diploid cells might be programmed, and/or that accumulation of genetic damage might limit proliferative capacity. They suggested that the limited proliferative lifespan of cell cultures was an expression of cellular aging in vitro.