Perspective on PCBs
Perspective on PCBs
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PCB 的观点
DOI：
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发表时间：
1972
影响因子：
10.4
通讯作者：
Basil Lee
中科院分区：
文献类型：
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作者：
Basil Lee
最后一位发言者是Alan Sinclair博士（英国威尔士卡迪夫）。他在1989年至1993年期间发现了127篇关于过早衰老的英文论文。研究的主要疾病为Werner综合征、Cockayne综合征和早衰症，美国和日本的产量居首位。虽然早衰症和正常衰老的过程有许多相似之处，但也有一些不一致之处。提示早衰症是一种散发性显性突变，可能以尿中透明质酸排泄增加为标志。无论如何，有一个与年龄相关的增加，但早衰症水平进一步提高。透明质酸作为蛋白聚糖存在于身体的许多基质中，并且对组织的稳定性很重要。在维尔纳综合征中，透明质酸的输出也会增加，死亡通常发生在第四个十年。从这些患者培养的成纤维细胞显示出较低的体外生长潜力，如S期细胞分数所示。似乎有一种基因调节剂可以提高细胞离开细胞周期死亡的频率。这样的成纤维细胞分泌更高水平的透明质酸到介质中比正常的，虽然透明质酸的降解速率不受影响，这表明增加的物质的合成。科凯恩综合征是隐性的，在生命的第二年变得明显。除了眼睛和骨骼异常，科凯恩患者还具有光敏性，这是因为细胞修复转录活性DNA中光损伤DNA的能力存在缺陷，其中受损的DNA不能被去除。在加速小鼠模型中，一个遗传易感群体，衰老被染色体异常、神经结构和功能异常、免疫学研究异常以及激素和生化缺陷所揭示。当对抗衰老和易衰老小鼠的结果进行比较的研究进行分析时，易衰老小鼠拥有一种类似于阿尔茨海默病中发现的蛋白质，这种蛋白质具有最初仅在高等哺乳动物中发现的颗粒结构，但现在也在小鼠中发现。Sinclair博士最后列出了研究PAS（过早衰老综合征）的一些困难，并概述了几条可能的研究路线。
The final speaker was Dr Alan Sinclair (Cardiff, Wales, UK). He had identified 127 papers in English on the subject ofpremature ageing between 1989 and 1993. The chief diseases studied were Werner's syndrome, Cockayne's syndrome and progeria, with the USA and Japan leading the field in output. Although there were many similarities between the processes in progeria and normal ageing there were also some discordances. The suggestion was that progeria was a sporadic dominant mutation with possibly an increased excretion of hyaluronic acid in the urine as a marker. There is an age-related increase anyway but progerioid levels were raised further. Hyaluronic acid is present in many matrices ofthe body as a proteo-glycan and is important in the stability of the tissues. In Werner's syndrome too there is an increased output of hyaluronic acid and death usually occurs in the fourth decade. Cultured fibroblasts from such patients show a lower potential for growth in vitro as shown by the fraction of cells in the S-phase. There seemed likely to be a gene modulator which enhanced the frequency at which cells left the cell cycle to die. Such fibroblasts secrete higher levels of hyaluronic acid into the media than normal although the rate of degradation of hyaluronic acid was not affected, suggesting an increased synthesis of the substance. The Cockayne syndrome was recessive, becoming manifest in the second year of life. Apart from eye and skeletal abnormalities Cockayne patients have photosensitivity, which lies in a defect in the ability of cells to repair photodamaged DNA in transscriptionally active DNA, where the damaged DNA cannot be removed. In the accelerated mouse model, a genetically susceptible population, senescence is betrayed by abnormalities in chromosomes, in nerve structure and function, in immunological studies and in hormonal and biochemical defects. When studies comparing results from senescence-resistant and senescence-prone mice are analysed the prone mice possess a protein like that found in Alzheimer's disease, a protein with a granular structure originally only identified in the higher mammals but now also found in mice. Dr Sinclair concluded by listing some ofthe difficulties in the investigation of the PAS (premature ageing syndrome) and outlined a few possible lines for research.