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Loss of cell identity drives human aging: Two new papers

369 points · 184 comments · bookofjoe

  1. dyauspitr · · focus · HN ↗
    So chronic stress is one of the main contributors to aging. I hope I make it to my 40s.

    Do we currently have the ability to do targeted methylation or de methylation at sites in cells?

    1. bglazer · · focus · HN ↗
      Yes we can do targeted (de)methylation at cells via a system called CRISPRon/off. It’s a CRISPR with the DNA cutting part deactivated but retaining the DNA binding part. They then attach a protein that adds methylation (DNMT3A) or removes it (TET1). So it’s a huge protein machine and it has only been tested in a petri dish (maybe mice, not sure).

      There’s a lot left to figure out. Delivery is hard. It would be hard to get it inside the right set of cells in a real person, you usually would only want to demethylate in a subset of cell types. There’s pretty steady progress being made in that area, but I think it will be several years before we fully solve that. Existing methods for doing this include hijacking a virus to deliver the DNA of the CRISPR system but those are one time only treatments because your immune system recognizes the virus and destroys it after one treatment. We use these viral delivery systems for some gene therapy treatments in real patients now. It presents a pretty terrible conundrum for patients who have to choose taking their one shot on an experimental treatment which may not work. Brave people!

      Anyways, yes it is possible but it’s quite early in development.

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