Hayflick Leonard
Department of Anatomy, University of California, San Francisco, School of Medicine, P.O. Box 89, The Sea Ranch, CA 95497, USA.
Exp Gerontol. 2003 Nov-Dec;38(11-12):1231-41. doi: 10.1016/j.exger.2003.09.003.
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.
自20世纪初首次进行细胞培养以来，人们一直认为，所有培养的细胞只要条件合适，都能无限增殖。60年后，我们推翻了这一教条，发现正常细胞的增殖能力是有限的，只有异常细胞或癌细胞群体才能无限增殖。我们认为这些发现有助于我们理解衰老过程。如果像之前所认为的那样，正常细胞可以无限增殖，那么衰老变化就不可能起源于细胞内。我们的发现表明，恰恰相反，衰老变化确实起源于细胞内。随后发现的数百种在复制能力丧失之前出现的变化被解释为衰老变化，而复制的有限性则被视为寿命决定的一种表现。其他人随后的发现确定了控制正常细胞复制能力有限性的分子机制，以及永生癌细胞如何逃避这种必然性。因此，我们对衰老、寿命决定和癌症的理解中的关键事件已经被揭示出来。
