Its the long genes that stop working (update)

#21

I don’t know. The IC50 is 90 microMolar which is weaker than berberine/quercetin etc.

There are quite a lot of HDAC inhibitors around and I take a mixture. In fact I am running some experiments cycling HDAC inibition as well as acetyl-CoA levels. Hence I have a day on relatively low levels then a day with higher levels.

I am a little concerned about the side effects of high levels of an HDAC (not on the histone, but other side effects) hence I think cycling might be best.

The ones I am using have relatively short half lives (around 4-10 hours). Pterostilbene is quite long at 105 even longer than Rapamycin, however.

Ironically it appears that Resveratrol’s main effect might be as an HDAC inhibitor in that it actually inhibits the sirtuins.

In the end the question with HDAC inibitors is quite complex because you have the IC50, the bioavailability, the half life and the dose. In the end it is probably really something which can only be worked out finally through experimentation.

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#22

Steve Horvath and Morgan Levine might be able to confirm whether HDAC inhibitors have the potential to extend life or influence the epigenetic clock.

#23

Or the ITP.

My own experiments have led me to conclude that HDAC inhibition does add to gene expression.

Scene 1 2023-06-23_07-21-36
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You can see it in this photograph where the timing of the start of hair growth is indicated by the length of the hair. Two phases of high HDAC usage (and the rest of my stack which is quite complicated) have caused additional facial hair to start up.

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#24

Following on here from your comment on another thread about Luteolin being an HDACi.

Unfortunately full text isn’t freely available but in the abstract they inject luteonlin whereas I will be ingesting a 100mg capsule. I wonder how well it is absorbed and makes it past the liver?

I also wonder if it’s anti-inflammatory properties are related to that of being an HDAC or if it just happens to interact with multiple pathways.

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#25

I am not sure about the use of “anti-inflammatory”. I think this is often used when what is happening is a reversal of senescence.

I do think HDACis have a role in dealing with senescence and gene expression more generally (which is not surprising).

Because I think one of the main causes of age related diseases relates to gene expression I think HDACi s can mitigate against this.

An interesting personal effect is to make more facial hair grow beyond what I had for the previous 62 years.

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#26

I recently found this paper:

Which I think is more evidence that the long genes issue relates to something other than DNA damage.

Making the point, however, that in terms of mtDNA the issue is different.

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#27

@Joseph_Lavelle kindly sent me a link to this:

https://www.cell.com/trends/genetics/fulltext/S0168-9525(24)00027-1

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#28

Here’s an image from the paper that is very interesting

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#29

In the end if the genome stops functioning properly it will cause some problems.

My view is to get it to function and then see what the remaining issues are.

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