Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts
- Washington University School of Medicine, United States
- University of California Los Angeles, United States
Abstract
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.
Data availability
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Data from: Maintenance of Age in Human Neurons Generated by MicroRNA-based Neuronal Conversion of FibroblastsAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
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Data from: Maintenance of Age in Human Neurons Generated by MicroRNA-based Neuronal Conversion of FibroblastsAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
National Institutes of Health (DP2NS083372-01)
- Andrew S Yoo
Ellison Medical Foundation (AG-NS-0878-12)
- Andrew S Yoo
National Institutes of Health (K99/R00, 4R00HL114732-03)
- Luis FZ Batista
Washington University in St. Louis (DDRCC, NIDDK P30 DK052574)
- Luis FZ Batista
National Institutes of Health (1U34AG051425-01)
- Steve Horvath
National Institutes of Health (5R01, AG042511-02)
- Steve Horvath
National Institute on Drug Abuse (R25 DA027995)
- Bo Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeremy Nathans, Johns Hopkins University School of Medicine, United States
Version history
- Received: June 9, 2016
- Accepted: September 15, 2016
- Accepted Manuscript published: September 20, 2016 (version 1)
- Version of Record published: October 17, 2016 (version 2)
Copyright
© 2016, Huh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts
eLife 5:e18648.
https://doi.org/10.7554/eLife.18648
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