title: Establishment of induced pluripotent stem cells from centenarians for neurodegenerative disease research.
abstract: 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.
authors: Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
authors: Takuya
authors: T
authors: Yagi
authors: Arifumi
authors: A
authors: Kosakai
authors: Daisuke
authors: D
authors: Ito
authors: Yohei
authors: Y
authors: Okada
authors: Wado
authors: W
authors: Akamatsu
authors: Yoshihiro
authors: Y
authors: Nihei
authors: Akira
authors: A
authors: Nabetani
authors: Fuyuki
authors: F
authors: Ishikawa
authors: Yasumichi
authors: Y
authors: Arai
authors: Nobuyoshi
authors: N
authors: Hirose
authors: Hideyuki
authors: H
authors: Okano
authors: Norihiro
authors: N
authors: Suzuki
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D020961:Lewy Body Disease / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D051844:alpha-Synuclein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors; D051844:alpha-Synuclein