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Reprogramming to recover youthful epigenetic information and restore vision
Yuancheng Lu1, Benedikt Brommer2,3, Xiao Tian1
1Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA.
Nature
|December 3, 2020
Summary
Scientists restored youthful epigenetic patterns in mouse eyes using specific gene reprogramming. This improved vision and nerve regeneration, suggesting tissues retain information to reverse aging effects.
Area of Science:
- Epigenetics and aging research
- Neuroscience and regenerative medicine
- Molecular biology and gene expression
Background:
- Aging leads to tissue dysfunction and loss of regenerative capacity, partly due to accumulating epigenetic noise.
- DNA methylation patterns change with age, forming the basis of aging clocks.
- It remains unknown if aged tissues retain information to restore youthful epigenetic patterns and improve function.
Purpose of the Study:
- To investigate if reprogramming specific genes in aged mouse retinal cells can restore youthful epigenetic patterns and function.
- To determine if this reprogramming can enhance tissue regeneration and reverse age-related vision loss.
- To explore the role of DNA demethylases TET1 and TET2 in OSK-induced reprogramming benefits.
Main Methods:
- Ectopic expression of Oct4 (Pou5f1), Sox2, and Klf4 genes (OSK) in mouse retinal ganglion cells.
- Analysis of DNA methylation patterns and transcriptomes to assess epigenetic restoration.
- Evaluation of axon regeneration after injury and vision restoration in glaucoma and aged mice models.
- Investigating the necessity of TET1 and TET2 DNA demethylases for observed functional improvements.
Main Results:
- OSK gene expression restored youthful DNA methylation patterns and transcriptomes in aged retinal cells.
- Reprogramming promoted axon regeneration following injury and reversed vision loss in glaucoma and aged mice.
- The pro-regenerative and vision-restoring effects of OSK were dependent on the DNA demethylases TET1 and TET2.
Conclusions:
- Mammalian tissues retain a record of youthful epigenetic information, partly encoded by DNA methylation.
- This epigenetic information can be accessed through gene reprogramming to improve tissue function and promote regeneration in vivo.
- Targeting epigenetic mechanisms offers a potential strategy for combating age-related decline and enhancing regenerative capacity.
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