近日，美国《公共科学图书馆—综合》（PLoS ONE）发表了日本庆应大学一个研究小组的研究成果，他们利用两名健康百岁老寿星死后的皮肤细胞，成功培育出诱导多功能干细胞（iPS细胞）。它们可以作为“无疾而终”的“正常细胞”的指标，用于帮助阿尔茨海默氏症等疾病的早期诊断。
据日本《产经新闻》网站7月26日报道，皮肤细胞在人死后大约两天内依然“存活”，庆应大学教授铃木则宏等人征得家属的同意后，从两名105岁以上的“健康长寿”死者身上分别采集了皮肤细胞，并且培育出了没有疾病性质的正常的iPS细胞，而且使其分化成神经细胞。
用阿尔茨海默氏症患者iPS细胞培育出的神经细胞与这些神经细胞相比，前者与疾病相关的一种蛋白质“β－淀粉肽”是后者的近两倍。用帕金森氏症患者iPS细胞培育出的神经细胞，其蛋白质“α－突触核蛋白”也是用这些“无疾终老”者iPS细胞培育出的神经细胞的近两倍。
由于样本采集自没有重病、极其健康的高寿老人遗体，用它们作为比照对象，有望帮助阿尔茨海默氏症等疾病的早期诊断，或帮助医学人员开发出相关疾病的早期预防药物。（生物谷Bioon.com）
doi:10.1371/journal.pone.0041572
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Establishment of Induced Pluripotent Stem Cells from Centenarians for Neurodegenerative Disease Research
Takuya Yagi1, Arifumi Kosakai1, Daisuke Ito1*, Yohei Okada2,3, Wado Akamatsu2, Yoshihiro Nihei1, Akira Nabetani4, Fuyuki Ishikawa4, Yasumichi Arai5, Nobuyoshi Hirose2, Hideyuki Okano2, Norihiro Suzuki1
Induced pluripotent stem cell (iPSC) technology can be used to model human disorders, create cell-based models of human diseases, including neurodegenerative diseases, and in establishing therapeutic strategies. To detect subtle cellular abnormalities associated with common late-onset disease in iPSCs, valid control iPSCs derived from healthy donors free of serious late-onset diseases are necessary. Here, we report the generation of iPSCs from fibroblasts obtained immediately postmortem from centenarian donors (106- and 109-years-old) who were extremely healthy until an advanced age. The iPSCs were generated using a conventional method involving OCT4, SOX2, KLF4, and c-MYC, and then differentiated into neuronal cells using a neurosphere method. The expression of molecules that play critical roles in late-onset neurodegenerative diseases by neurons differentiated from the centenarian-iPSCs was compared to that of neurons differentiated from iPSCs derived from familial Alzheimer's disease and familial Parkinson's disease (PARK4: triplication of the α synuclein gene) patients. The results indicated that our series of iPSCs would be useful in neurodegeneration research. The iPSCs we describe, which were derived from donors with exceptional longevity who were presumed to have no serious disease risk factors, would be useful in longevity research and as valid super-controls for use in studies of various late-onset diseases.
