Living forever and dying in the attempt

Since the first cell culture was set at the beginning of the twentieth century it was believed that all cultured cells, if provided with the proper conditions, would replicate indefinitely. Sixty years later we overthrew this dogma by finding that normal cells have a finite capacity to replicate and that only abnormal or cancer cell populations can replicate indefinitely. We interpreted these findings to bear on our understanding of the aging process. If, as had been previously thought, normal cells can replicate indefinitely, then age changes could not have an intracellular origin. Our findings demonstrated that, on the contrary, age changes do have an intracellular origin. The hundreds of changes that were subsequently found to precede the loss of replicative capacity have been interpreted to be age changes and the finitude of replication to be an expression of longevity determination. Subsequent findings by others have determined the molecular mechanism that governs the finitude of normal cell replicative capacity and how immortal cancer cells escape this inevitability. Thus, key events in our understanding of aging, longevity determination and cancer have been revealed. (C) 2003 Elsevier Inc. All rights reserved.