Fixed mortality of normal somatic cells is a well-established fact though the mechanism underlying this universal phenomenon remains unknown. Use of immortal cells in conjunction with their normal mortal counterparts has delineated the dominant genetic nature of the senescent phenotype over immortalization. Although the involvement of proteins in determining the entry/exit/arrest of cells in the cell cycle is evident from the literature, none of them has been confirmed for its role in senescence-associated irreversible cell cycle exit/arrest. The identification of true mortality markers might be possible by selecting a system of natural and conditional aging achieved by the fusion of mortal and spontaneously immortalized cells of the same origin. We report here a few such protein markers which might serve as useful handles to tease out the molecular events determining mortality/immortality of cultured cells.