Australian Academy of Science, Canberra, Australia.
Sci Prog. 2012;95(Pt 2):199-205. doi: 10.3184/003685012X13361526995348.
It is not always realised that separate fibroblast populations of the same strain have very different lifespans, that is, over a million-fold range. This is best documented for human strains WI-38 and MRC-5. There is evidence that it is the molecular clock of telomere shortening which determines the growth potential of these cells. However, if a clock is set and runs its course one would expect parallel cultures to have similar lifespans. The commitment theory of fibroblast ageing proposes that commitment occurs during early cell divisions with a given probability and after that there is then a constant number of divisions until growth ceases. This constant number could be determined by the gradual loss of telomeres. The stochastic feature of the theory is the probability of the loss of the last uncommitted cells or the youngest committed cells. These cells have the longest lifespan and will give rise to the final population.
人们并不总是意识到同一株的不同成纤维细胞群体具有非常不同的寿命,即相差一百万倍。这在 WI-38 和 MRC-5 这两个人类株系中得到了最好的证明。有证据表明,是端粒缩短的分子钟决定了这些细胞的生长潜力。然而,如果设置了一个时钟并让其运行,人们会期望平行培养物具有相似的寿命。成纤维细胞衰老的承诺理论提出,在给定的概率下,在早期细胞分裂中发生承诺,之后直到生长停止,就会有一个固定数量的分裂。这个固定数量可能由端粒的逐渐丢失决定。该理论的随机特征是最后一个未承诺细胞或最年轻的承诺细胞丢失的概率。这些细胞具有最长的寿命,并将产生最终的群体。