Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts
Open Access
- 20 September 2016
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
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.Keywords
Funding Information
- National Institute on Drug Abuse (R25 DA027995)
- National Institutes of Health (K99/R00)
- Washington University in St. Louis (DDRCC)
- National Institutes of Health (4R00HL114732-03)
- Washington University in St. Louis (NIDDK P30 DK052574)
- National Institutes of Health (1U34AG051425-01)
- National Institutes of Health (5R01, AG042511-02)
- National Institutes of Health (DP2NS083372-01)
- Ellison Medical Foundation (AG-NS-0878-12)
- Cure Alzheimer's Fund
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