Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts
Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a rec...
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doaj-29d75ef1e2dd4bf6a657f8c782e978992021-05-05T00:35:34ZengeLife Sciences Publications LtdeLife2050-084X2016-09-01510.7554/eLife.18648Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblastsChristine J Huh0Bo Zhang1Matheus B Victor2Sonika Dahiya3Luis FZ Batista4Steve Horvath5Andrew S Yoo6https://orcid.org/0000-0002-0304-3247Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Program in Molecular and Cellular Biology, Washington University School of Medicine, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Program in Neuroscience, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Department of Medicine, Washington University School of Medicine, St. Louis, United StatesDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United StatesAging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnatal to near centenarian donors can be efficiently converted into neurons that maintain multiple age-associated signatures. Application of an epigenetic biomarker of aging (referred to as epigenetic clock) to DNA methylation data revealed that the epigenetic ages of fibroblasts were highly correlated with corresponding age estimates of reprogrammed neurons. Transcriptome and microRNA profiles reveal genes differentially expressed between young and old neurons. Further analyses of oxidative stress, DNA damage and telomere length exhibit the retention of age-associated cellular properties in converted neurons from corresponding fibroblasts. Our results collectively demonstrate the maintenance of age after neuronal conversion.https://elifesciences.org/articles/18648agingneuronal conversionhuman neurons |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christine J Huh Bo Zhang Matheus B Victor Sonika Dahiya Luis FZ Batista Steve Horvath Andrew S Yoo |
spellingShingle |
Christine J Huh Bo Zhang Matheus B Victor Sonika Dahiya Luis FZ Batista Steve Horvath Andrew S Yoo Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts eLife aging neuronal conversion human neurons |
author_facet |
Christine J Huh Bo Zhang Matheus B Victor Sonika Dahiya Luis FZ Batista Steve Horvath Andrew S Yoo |
author_sort |
Christine J Huh |
title |
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts |
title_short |
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts |
title_full |
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts |
title_fullStr |
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts |
title_full_unstemmed |
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts |
title_sort |
maintenance of age in human neurons generated by microrna-based neuronal conversion of fibroblasts |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2016-09-01 |
description |
Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnatal to near centenarian donors can be efficiently converted into neurons that maintain multiple age-associated signatures. Application of an epigenetic biomarker of aging (referred to as epigenetic clock) to DNA methylation data revealed that the epigenetic ages of fibroblasts were highly correlated with corresponding age estimates of reprogrammed neurons. Transcriptome and microRNA profiles reveal genes differentially expressed between young and old neurons. Further analyses of oxidative stress, DNA damage and telomere length exhibit the retention of age-associated cellular properties in converted neurons from corresponding fibroblasts. Our results collectively demonstrate the maintenance of age after neuronal conversion. |
topic |
aging neuronal conversion human neurons |
url |
https://elifesciences.org/articles/18648 |
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