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AdamMarblestone's profile
Adam Marblestone
Adam Marblestone
Adam Marblestone
@AdamMarblestone

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Adam Marblestone

@AdamMarblestone

Technologist, Scientist

adammarblestone.org
Joined February 2009

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    1. José Luis Ricón Fernández de la Puente‏ @ArtirKel May 26
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      @AdamMarblestone @s_r_constantin All these clocks are looking at CpG methylation. But.. non-CpG methylation is also a thing, and seems to matter in the brainhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/ …

      1 reply 0 retweets 1 like
    2. Martin Borch Jensen‏ @MartinBJensen May 26
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      Replying to @ArtirKel @AdamMarblestone @s_r_constantin

      Original clocks weren't looking for anything but correlation with age, presumably used CpG because more abundant so easier to measure. I'm about a year out of date but I don't think we are (yet) saying much about the biological effects of these methylation changes.

      1 reply 0 retweets 0 likes
    3. José Luis Ricón Fernández de la Puente‏ @ArtirKel May 26
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      Replying to @MartinBJensen @AdamMarblestone @s_r_constantin

      The papers I've been looking at are largely correlational; newer clocks are looking at more than age (hazard ratios for mortality is the new thing in GrimAge and PhenoAge). What would be a good way to measure causality here?

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    4. Martin Borch Jensen‏ @MartinBJensen May 26
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      Replying to @ArtirKel @AdamMarblestone @s_r_constantin

      Right and at least one paper looked at response to common #aging treatments (#InMice). But still corr. One approach to causation is to use eg Cas9 fusion to add/remove methylation at the few sites with largest impact on models (I think <10s).

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    5. José Luis Ricón Fernández de la Puente‏ @ArtirKel May 26
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      Replying to @MartinBJensen @AdamMarblestone @s_r_constantin

      And does methylation editing stay in place? If you take a methyl away, wait a /some week(s) and measure again, will that site look like that of a control mice?

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    6. Martin Borch Jensen‏ @MartinBJensen May 26
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      Replying to @ArtirKel @AdamMarblestone @s_r_constantin

      Cells will override it given stimuli (we don't understand), but w persistent expression of your CRISPR stuff I'd guess you'd have persistent demethylation. NB if you wanted to do this #InVivo you'd prob want to use a mouse with the Cas9 engineered in, to avoid immune response.

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      Adam Marblestone‏ @AdamMarblestone May 26
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      Replying to @MartinBJensen @ArtirKel @s_r_constantin

      Cool. And can CRISPR activate or inactivate other genes while you’re at it if you think there is more that needs to happen than methylation changes, to drive the system. A few orthogonal Cas9’s engineered in but many mice getting many different cocktails of gRNAs at embryo stage!

      5:36 PM - 26 May 2020
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        2. Adam Marblestone‏ @AdamMarblestone May 26
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          Replying to @AdamMarblestone @MartinBJensen and

          p.s., of course in addition to methylation there are lots of other epigenetic assays like HiC, transcriptome itself, and so on... which could maybe make clocks... maybe an exosome RNA clock...

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        3. Adam Marblestone‏ @AdamMarblestone May 26
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          Replying to @AdamMarblestone @MartinBJensen and

          Add persistent maintenance of the DNA encoding your gRNAs but make it all drug inducible and you have a hell of a platform for combinatorial i/o for aging

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        4. End of conversation

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