Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation

Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation
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DOI:
10.1073/pnas.95.18.10614
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发表时间:
1998-09-01
影响因子:
11.1
通讯作者:
Beck, JC
Beck, JC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cristofalo, VJ;Allen, RG;Beck, JC

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正常人二倍体成纤维细胞在体外具有有限的复制寿命,这被假定为体内衰老的细胞表现。几项研究表明,供体年龄和成纤维细胞培养复制寿命之间呈反比关系;然而,在所有情况下,相关性都很弱,而且,除了少数例外,供体的健康状况不明。作为巴尔的摩老龄化纵向研究的一部分,我们测定了从不同年龄供体中建立的124个皮肤成纤维细胞系的复制寿命。根据巴尔的摩老龄化纵向研究方案,在进行活检时,所有供体都进行了医学检查并被宣布为“健康”。在所有年龄组中均观察到长寿命和短寿命的细胞系,但细胞系的增殖潜力与供体年龄之间无显著相关性,对不同年龄的相同供体建立的多个细胞系进行比较也未能揭示增殖潜力与供体年龄之间的任何显著趋势。在一个亚组的细胞系中检查了[H-3]胸苷掺入率和最初几次传代培养期间的初始生长率,发现胎儿系中的[H-3]胸苷掺入率和最初几次传代培养期间的初始生长率显著高于出生后系。从成人建立的细胞系在初始生长率或[H-3]胸苷掺入率方面没有显著变化。这些结果清楚地表明,如果健康状况和活组织检查条件得到控制,培养的成纤维细胞的复制寿命与供体年龄无关。
Normal human diploid fibroblasts have a finite replicative lifespan in vitro, which has been postulated to be a cellular manifestation of aging in vivo. Several studies have shown an inverse relationship between donor age and fibroblast culture replicative lifespan; however, in all cases, the correlation was weak, and, with few exceptions, the health status of the donors was unknown. We have determined the replicative lifespans of 124 skin fibroblast cell lines established from donors of different ages as part of the Baltimore Longitudinal Study of Aging, All of the donors were medically examined and were declared "healthy," according to Baltimore Longitudinal Study of aging protocols, at the time the biopsies were taken. Both long- and short-lived fell lines were observed in all age groups, but no significant correlation between the proliferative potential of the cell lines and donor age was found. A comparison of multiple cell lines established from the same donors at different ages also failed to reveal any significant trends between proliferative potential and donor age. The rate of [H-3]thymidine incorporation and the initial rates of growth during the first few subcultivations were examined in a subset of cell lines and were found to be significantly greater in fetal lines than in postnatal lines, Cell lines established from adults did not vary significantly either in initial growth rate or in [H-3]thymidine incorporation, These results clearly indicate that, if health status and biopsy conditions are controlled, the replicative lifespan of fibroblasts in culture does not correlate with donor age.