Cell senescence: role in aging and age-related diseases.

Cell senescence: role in aging and age-related diseases.
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DOI:
10.1159/000358899
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发表时间:
2014
期刊:
Interdisciplinary topics in gerontology
影响因子:
--
通讯作者:
Robert L
Robert L
中科院分区:
其他
文献类型:
--
作者:
Campisi J;Robert L

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理解衰老,正如人们所感受到的,医学通过与年龄有关的疾病来研究衰老,是人类和研究的一个古老的关注点。为了了解其多方面,传统的实验医学“方法”,模型实验是至关重要的。当细胞组织培养方法被开发出来时,这在很大程度上得到了促进。目前的细胞组织培养方法是在20世纪下半叶才发展起来的,除了一些早期的尝试,我们将很快提到。早期的研究是由来自里昂的法国外科医生亚历克西斯·卡雷尔(Alexis Carrel)进行的,他在纽约市洛克菲勒研究所(Rockefeller Institute)工作了大部分时间。他使用了鸡胚的外植体培养,将其保存在含有血浆和鸡胚提取物的营养培养基中,这种培养基是通过研磨小鸡胚和使用这种组织悬浮液的滤液获得的。他证明了鸡胚胎心脏外植体可以在很长一段时间内继续跳动,肌肉外植体可以在刺激下收缩。卡雷尔对衰老很感兴趣,他注意到这种外植体培养物可以在37摄氏度的无菌条件下保存,比动物的预期寿命长得多。他的结论是,疾病和死亡主要是由体液引起的,体液会随着年龄的增长而逐渐改变,并损害机体。20世纪60年代,莱恩·海弗利克对细胞培养进行了重要的观察,表明正常的、未转化的细胞不能无限分裂,成功地反驳了卡雷尔的观点。海弗利克的发现并没有被立即接受。他仔细调查了卡雷尔的方法,甚至采访了卡雷尔的一位前技术人员,这位技术人员已在“殖民地”退休。她告诉海弗利克,胚胎提取物必须在里昂准备好,然后用飞机运送到卡雷尔在纽约的实验室。由于在制备过程中使用组织(纱布)过滤,它可能含有新鲜的活细胞,因此可以解释培养物的明显无限存活。其他试图重现卡雷尔发现的科学家无一例外地失败了,海弗利克的范式逐渐被接受,但也免不了遭到反复的否认和批评。大多数按照海弗利克发表的指导方针工作的科学家都能重现他的结果。在上世纪下半叶,细胞和组织培养方法变得标准化,培养皿和培养基变得商业化。这在很大程度上促进了实验室间文化方法论的标准化,并确定了一个
To understand aging, as felt by persons, studied by medical science through age-related diseases, is an ancient preoccupation of humanity and research. In order to understand its multiple facets, the traditional “method” of experimental medicine, model experiments are of crucial importance. This was largely facilitated when cell-tissue culture methods were developed. Current methods for cell-tissue cultures were developed only during the second part of the 20th century, with the exception of some earlier attempts we shall shortly mention. Early studies were carried out by Alexis Carrel, a French surgeon from Lyon who worked during most of his carrier at the Rockefeller Institute in New York City. He used explant cultures of chicken embryos, maintained in a nutritional medium containing blood plasma and chick embryo extracts, obtained by grinding young chick embryos and using the filtrate of this tissue suspension. He showed that chick embryo heart explants could continue to beat, and muscle explants could contract upon stimulation, for a long time.Interested in aging, Carrel noticed that such explant cultures could be kept in sterile conditions at 37 C for much longer than the life expectancy of the animal. He concluded that disease and death are mainly due to body-fluids,“humors” which would progressively alter with age and harm the organism. Carrel was successfully contradicted in the nineteen sixties when Len Hayflick made his important observations on cell cultures and showed that normal, non-transformed cells cannot divide indefinitely. Hayflick’s findings were not immediately accepted. He investigated closely Carrel’s methodology and even interviewed a former technician of Carrel, retired in the “colonies”. She told Hayflick that the embryo extract had to be prepared in Lyon and delivered by airplane to Carrel’s lab in New York. As it was filtered during its preparation using a tissue (gauze), it could contain fresh living cells that thus could explain the apparently illimited survival of the cultures. Other scientists who attempted to reproduce Carrel’s findings, invariably failed and Hayflick’s paradigm was progressively accepted, not however without repeated denials and criticisms. Most scientists who worked according to the guidelines published by Hayflick could reproduce his results. During the 2nd part of the last century cell-and tissue culture methods became standardized, and culture dishes and media became commercially available. This largely contributed to the inter-laboratory standardization of culture-methodology and settled to a
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