Unbalanced Growth, Senescence and Aging.

Usually, cells balance their growth with their division. Coordinating growth inputs with cell division ensures the proper timing of division when sufficient cell material is available and affects the overall rate of cell proliferation. At a very fundamental level, cellular replicative lifespan-defined as the number of times a cell can divide, is a manifestation of cell cycle control. Hence, control of mitotic cell divisions, especially when the commitment is made to a new round of cell division, is intimately linked to replicative aging of cells. In this chapter, we review our current understanding, and its shortcomings, of how unbalanced growth and division, can dramatically influence the proliferative potential of cells, often leading to cellular and organismal aging phenotypes. The interplay between growth and division also underpins cellular senescence (i.e., inability to divide) and quiescence, when cells exit the cell cycle but still retain their ability to divide.