Holliday Robin
Australian Academy of Science, Canberra, Australia.
Interdiscip Top Gerontol. 2014;39:1-7. doi: 10.1159/000358896. Epub 2014 May 13.
Fifty years ago, it was demonstrated by Leonard Hayflick that human diploid fibroblasts grown in culture have a finite lifespan. Since that time, innumerable experiments have been published to discover the mechanism(s) that are responsible for this 'Hayflick limit' to continuous growth. Much new information has been gained, but there are certain features of this experimental system which have not been fully understood. One is the fact that different populations of the foetal lung strains WI-38 and MRC-5 have a range in division potential of at least a millionfold. The commitment theory of cellular aging, published more than 30 years ago, is able to explain this, but it has been consistently ignored. The theory predicts that bottlenecks, which are transient reductions in population size, can significantly reduce lifespan, or increase variability of lifespans. Computer simulations specify the effects of bottlenecks on longevity, and these were confirmed in two series of experiments. Commitment to senescence may be the loss of telomerase, which leads to the erosion of telomeres and the inability to grow indefinitely. Many experiments have been done with skin fibroblasts from human donors of different age, and it was originally thought that in vitro lifespan was inversely correlated with donor age. In these experiments, a single skin biopsy produces a population of cells that are grown to senescence. However, there is no reason to believe that skin fibroblasts are less variable in their in vitro lifespan than foetal lung strains, in which case the data points with skin cells are so variable that they may completely obscure any inverse correlation between culture lifespans and donor age.
五十年前，伦纳德·海弗利克证明，在培养中生长的人类二倍体成纤维细胞具有有限的寿命。从那时起，已经发表了无数实验来探寻导致这种连续生长的“海弗利克极限”的机制。虽然已经获得了许多新信息，但这个实验系统的某些特征尚未得到充分理解。其中之一是，胎儿肺细胞系WI-38和MRC-5的不同群体在分裂潜能上至少相差一百万倍。三十多年前发表的细胞衰老的承诺理论能够解释这一点，但一直被忽视。该理论预测，种群数量的短暂减少即瓶颈，会显著缩短寿命，或增加寿命的变异性。计算机模拟明确了瓶颈对寿命的影响，这在两个系列的实验中得到了证实。对衰老的承诺可能是端粒酶的丧失，这会导致端粒侵蚀以及无法无限生长。已经对来自不同年龄人类供体的皮肤成纤维细胞进行了许多实验，最初认为体外寿命与供体年龄呈负相关。在这些实验中，单次皮肤活检产生一群生长至衰老的细胞。然而，没有理由相信皮肤成纤维细胞在体外寿命方面的变异性比胎儿肺细胞系小，在这种情况下，皮肤细胞的数据点变化如此之大，以至于它们可能完全掩盖了培养寿命与供体年龄之间的任何负相关关系。
