Although the fundamental mechanisms of in vitro cell aging are still undetermined, certain prominent features have emerged that serve to delineate or focus the search for these mechanisms. In Table 3.1 we present a selected list of changes that accompany senescence in culture. As cells get older they get bigger (Cristofalo & Kritchevsky, 1969) in general, although the synthesis rate of all macromolecules goes down (Houck, Sharma, & Hayflick, 1971; Macieira-Coelho, Ponten, & Phillipson, 1966), the cellular content of macromolecules other than deoxyribonucleic acid (DNA) goes up (Cristofalo & Kritchevsky, 1969; Cristofalo et al., 1970). This is a situation reminiscent of the phenomenon of unbalanced growth in bacteria, which was described more than 30 years ago (Cohen & Barner, 1954). In this situation all processes except the ability to synthesize DNA proceed, albeit not at the normal rate. It appears that DNA synthesis becomes uncoupled from other macromolecular syntheses, and there is a general disintegration of regulation as the cells proceed through the cell cycle.