DNA methylation and de-methylation - Crispr

For those interested on Crispr and it’s potential to make changes to methylation.

“In the future, using these tools to establish direct links between transcriptional regulation and DNA methylation status will enable us to decipher the precise role of epigenetic modification in health and disease and will increase our overall understanding of the human genome.“

https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1566-

Link appears broken try this one

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219187/

When a CpG island in the promoter region of a gene is methylated , expression of the gene is repressed (it is turned off ). The addition of methyl groups is controlled at several different levels in cells and is carried out by a family of enzymes called DNA methyltransferases (DNMTs).

From Melcangis study

Results: SRD5A1 and SRD5A2 methylation analysis was performed in all blood samples (n = 16 PFS patients and n = 20 controls), in 16 CSF samples from PFS patients and in
13 CSF samples from controls. The SRD5A2 promoter was more frequently methylated
in CSF of PFS patients compared to controls (56.3 vs 7.7%). No promoter methylation
was detected in blood samples in both groups. No methylation occurred in the SRD5A1 promoter of both groups. Unmethylated controls compared to unmethylated SRD5A2 patients showed higher pregnenolone, dihydrotestosterone and dihydroprogesterone, together with lower testosterone CSF levels. Andrological and neurological assessments did not differ between methylated and unmethylated subjects.

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Honestly was worried for a second there everyone thought this was a gut or immune system problem. Thanks I love reading this stuff.

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Nice find! It gives a nice graphical overview of the use of CRISPR and other biotech to alter DNA methylation.

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Ha. Yes, its always good not to make too many assumptions. You know what they say about the word assume?
Maybe its what ails a person most?
I wouldnt ignore the fact that it seems like half the people on here cant even shit right.
Im not sure if lack of androgen action is the first conclusion to come to here.
Some are convinced its a dopamine issue, androgen issue, gut, immunity, a serotonin issue.
With Accutane a possible vitamin toxicity issue if you check the other website.

People will believe what they want to believe, but at the end of the day this could be part hallucination or a coping mechanism as they search for answers (im not exempt from this).

I would also say even though there might be some common ground, these drugs are not interchangeable.
If being dismissive maybe we should give better reasoning then “just because” as a means to progress.

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Microbiome alterations have been proven.

I used to make beautiful heavy stools and felt like a new man when I squeezed one out (which was a lot of work)

For years now my stools are soft, diabolical smelling, light and airy, and leave a nasty residue. Quite different than the glorious turds of the past.

I am certain that our guys are messed up. @towm8er who cured himself, focused greatly on the gut.

“All disease begins in the gut.”

-Hippocrates

I’ve been taking butyrate before bed every night and I can say that my poops have gone from what you describe everyday to very normal. As for my symptoms it hasn’t done much but it’s only been a week or two. @Sawproblemo

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That’s still pretty encouraging. It may take time to give you the symptom improvement as I don’t think the gut microbiome can be restored quickly. I think a few members are cured or significantly improved from butyrate. I’m going to stick to simple diet for now. Trying to make homemade kefir but I think I’m doing it wrong. I bet a few months of the kefir and kombucha will restore my shits

Yea I’m taking it because @MOONCHILD said he’s a lot better now after doing butyrate and bhb

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I respect other people have their theories, I usually stay away from “gut threads” I don’t come barging in with my opinions for the most part. If I said what I really thought I’m sure I would offend a lot of people. The absolute last thing I wanted was for this to become a “gut thread” which it appears I have mistakenly done. Sorry guys.

Anyway the gut is one of those guys you can kind of blame for everything and it’s been a huge one size fits all theory for a lot of diseases. However it’s not the cause for all disease, and in recent years there has been a fad/cult like movement. I believe a lot of health issues and disease are caused by the gut, yes. This one? No. Again my belief. Not trying to trigger anyone.

I never ignored this fact once to be fair. Androgen receptors are in the gut, which means they have a pretty important role there. Androgens also control other neurotransmitter systems in the brain and body to give a cascade effect of all sorts of symptoms.

It is also to be noted butyrate is a demethylating agent.

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Another reason why I’m taking it, it in theory should help our situation whether it be gut or Epigenetic.

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Cover all bases :ok_hand:

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This is exciting news. I’d happily be a CRISPR guinea pig.

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Thanks. I see spots where I feel like saying something sometimes. Its not really based on personal thoughts but maybe clarification?
I see a separation of epigenetic modification, immune regulation and intestinal homeostasis, when there is a good possibility all three of these processes could be closely interlinked.

I could regurgitate a lot of already posted thoughts on the subject here, but I dont really see a point in that atm.
As far as androgens regulating the digestive tract, you’ll find a few recent articles on the subject, but you’ll run out of these pretty quick. Not that there couldnt be a problem with muscular function here.

As far as epigenetic modification,
Apparently a person can do literally nothing to have an impact on DNA expression.
Changes in diet, sun exposure, the microbiome, astronauts in space, can all have a major impact on DNA expression, and oh btw drugs as well or xenobiotics.

Meditation and yoga can ‘reverse’ DNA reactions which cause stress, new study suggests

There was another thread started recently about how do you heal yourself?
I think it might be more about how do you protect yourself from these environmental exposures?
They say heart disease is only 15% genetics. How do you protect from heart disease, diabetes, neurodegeneration, cancer, stroke, drug exposures, endocrine disruptors?
What were you 8 pills 10 years ago?
Thats why maybe this becomes a life issue, not just a drug one.
Some of you are losing the war. How do you stop the bleeding?
Thats a question I ask myself anyways.

Not sure what you mean by this. I’d prefer not to be personally attacked.

Sorry I’m not trying to attack you but was trying to make a point that I must have lost. I’ve said this before, maybe we don’t focus on our drug itself and how they might relate, rather how we relate.

Before my crash I noticed the gut was the first warning and my stools changed overnight. PFS is like advanced old age. Experts are now looking at methylation as a cause of such issues. So perhaps methylation is like a rope that’s wrapped around something squeezing it tightly and not allowing our hormones to get through. The least affected are probably able to get enough hormones through were they can exercise and do things that influence methylation. Overtime the rope begins to loosen up allowing more hormones to come through. That’s why some are able to recover with a lifestyle that influences methylation and they reverse PFS. Sibelio has posted his theory on the two types of PFS. The methylation is the worst one. The other type a HPTA crash allows for a good recovery in a few years.
I think the way forward is to develop protocols around methylation and link in the different ideas that influence these. It’s likely going to take multiple methods to see improvements. So rather than get hopeful about one method and then get upset when it doesn’t work make it part of a multiple group of ideas.
These drugs likely caused very powerful responses to methylation in a short amount of time. So far we have not seen something that is equally as strong that can reverse PFS symptoms in the same time frame.
In the other post I made on Crispr it showed that it could reverse disease almost overnight. That’s what we need here. If we could loosen up the stranglehold on our hormones it may then be enough to overcome the rest with natural therapies.
This is in relation to damaged hormones like T and DHT. How it fixes issues in the brain I don’t know. We may never have the answer to this until someone’s brain is opened up by a scientist.
However methods to reverse old age that tie into methylation should be a topic worth pursuing on here. It could even be worthy of its own section on the forum.

What is the epigenetic age of those of us with PFS symptoms?

https://www.activemotif.com/blog-reversing-epigenetic-age

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What if Crispr was able to demethylate the 5ar gene and in a perfect world DHT started to function normally. Wouldn’t the body detect a sudden influx of DHT at abnormal levels and shut down again? As with any cure for PFS won’t we be faced with this problem no matter what fixes PFS? Too much DHT and the body shuts down. So is this condition now incurable? Sorry this is jumping ahead but just wondering if anyone had a theory on this.

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Your posts seem confusing to me, like lots of open ended questions and information but I’m not sure what point you are getting at? Not being rude, maybe this was your purpose?

Yes they’re all linked, the point here is what came first that is effecting everything else. To find a cure we have to find the root cause, no?

It’s not really about articles, it doesn’t matter how many articles there are. There’s receptors in the gut, they have a function. Without them the function fails. Not sure there’s anymore to it?

I’m aware of everything epigenetic that you have mentioned. There’s many types of epigenetic alterations, some being reversible and some being permanent. It’s only when they are significant that we would notice something has gone wrong. These articles are In a sense useless. Of course these things effect epigenetics (excercise, yoga, life events) but we need to reverse a specific and severe epigenetic change. This requires pinpointing it and finding something that effects it precisely. A serious alteration requires serious reversal. The epigenetic changes from yoga and exercise are not compareable to the changes from these drugs.

I always thought my problem was receptor based long before I hit this forum, due to my personal situation and how severely my brain now responded to natural increases and decreases of neurotransmitters. I can feel my problem so vividly, there’s no questions for me personally. For people who have weak symptoms or those who can cycle through supplements and treatments, I get why they have different theories. Those theories in reguards to what I have are laughable to me. Coming here and seeing some admins had similar conclusions but with many more answers to the intricacies of my reactions than I had the knowledge to explain at the time, was quite liberating. Finally someone understood me.

I agree that these pills were indeed an “environmental exposure” that our genetics weren’t programmed to deal with. Unfortunately we can’t go back in time and avoid them.

Yes more questions than answers, if I was on here to play the role of Mr. Right, I wouldn’t really trust that.
As far as anything else, its All good.

Apparently there’s a guy getting crispr treatment for a special type of blindness, in the USA