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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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Autores principales: Huh, Christine J, Zhang, Bo, Victor, Matheus B, Dahiya, Sonika, Batista, Luis FZ, Horvath, Steve, Yoo, Andrew S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067114/
https://www.ncbi.nlm.nih.gov/pubmed/27644593
http://dx.doi.org/10.7554/eLife.18648
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author Huh, Christine J
Zhang, Bo
Victor, Matheus B
Dahiya, Sonika
Batista, Luis FZ
Horvath, Steve
Yoo, Andrew S
author_facet Huh, Christine J
Zhang, Bo
Victor, Matheus B
Dahiya, Sonika
Batista, Luis FZ
Horvath, Steve
Yoo, Andrew S
author_sort Huh, Christine J
collection PubMed
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. DOI: http://dx.doi.org/10.7554/eLife.18648.001
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spelling pubmed-50671142016-10-19 Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts Huh, Christine J Zhang, Bo Victor, Matheus B Dahiya, Sonika Batista, Luis FZ Horvath, Steve Yoo, Andrew S eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.18648.001 eLife Sciences Publications, Ltd 2016-09-20 /pmc/articles/PMC5067114/ /pubmed/27644593 http://dx.doi.org/10.7554/eLife.18648 Text en © 2016, Huh et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Huh, Christine J
Zhang, Bo
Victor, Matheus B
Dahiya, Sonika
Batista, Luis FZ
Horvath, Steve
Yoo, Andrew S
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts
title 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_short 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
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067114/
https://www.ncbi.nlm.nih.gov/pubmed/27644593
http://dx.doi.org/10.7554/eLife.18648
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