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4-OHT and reversal of skin aging


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#1 Gandy

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Posted 16 May 2008 - 02:21 PM


I'm surprised there isn't more discussion of this study:


http://www.genesdev....full/21/24/3244

Does anyone know how one would go about procuring 4-OHT? Or is it prescription only?

#2 drunkfunk

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Posted 16 May 2008 - 10:42 PM

I'm surprised there isn't more discussion of this study:


http://www.genesdev....full/21/24/3244

Does anyone know how one would go about procuring 4-OHT? Or is it prescription only?

i'm wondering the same thing.
don't you guys wanna be millionaeres?
but seriously, would this really work?
and what also confuses me, wouldn't the nf-kappa-b-inhibition actually lessen cancer-worries? because they talk about how long-term it may actually promote it?

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#3 niner

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Posted 16 May 2008 - 11:43 PM

I'm surprised there isn't more discussion of this study:

http://www.genesdev....full/21/24/3244

Does anyone know how one would go about procuring 4-OHT? Or is it prescription only?

It wouldn't be that hard to get 4-OHT, but I doubt that it would do much for you, unless you are transgenic... These mice had a 4-OHT-responsive transgene that would essentially shut off production of NFKB. So we are all out of luck until someone can figure out how to knock down NFKB without genetic modification.

#4 caston

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Posted 18 May 2008 - 03:09 AM

I'm surprised there isn't more discussion of this study:

http://www.genesdev....full/21/24/3244

Does anyone know how one would go about procuring 4-OHT? Or is it prescription only?

It wouldn't be that hard to get 4-OHT, but I doubt that it would do much for you, unless you are transgenic... These mice had a 4-OHT-responsive transgene that would essentially shut off production of NFKB. So we are all out of luck until someone can figure out how to knock down NFKB without genetic modification.



And if we do find a way please don't let yourself or anyone get any ideas about being a guinea pig. We are the immortality institute not the mortality institute.

#5 niner

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Posted 18 May 2008 - 03:54 AM

I'm surprised there isn't more discussion of this study:

http://www.genesdev....full/21/24/3244

Does anyone know how one would go about procuring 4-OHT? Or is it prescription only?

It wouldn't be that hard to get 4-OHT, but I doubt that it would do much for you, unless you are transgenic... These mice had a 4-OHT-responsive transgene that would essentially shut off production of NFKB. So we are all out of luck until someone can figure out how to knock down NFKB without genetic modification.


And if we do find a way please don't let yourself or anyone get any ideas about being a guinea pig. We are the immortality institute not the mortality institute.

Apparently NFKB is needed during development. After that, it seems to mainly be a bad actor, being involved in inflammation and cancer. About the only useful function of it that I know of is in immune response to certain insults. There are a lot of people looking at ways to inhibit it, and inhibitors exist. Now that this result has come out, I would not be surprised if some people start looking at those inhibitors in topical applications. Resveratrol is an NFKB inhibitor, IIRC. We've already had some topical resveratrol Guinea pigs. No one's died that I know of...

And this would be my 2000th post! What do I win? Another star?

#6 caston

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Posted 18 May 2008 - 04:17 AM

Well NFKB inhibition will effect metabolism. Inflammation is a defensive (self offensive) and healing response. While reducing phagoctye numbers may be benefical we are talking a lot of complicated and little understood interconnecting pathways in human metabolism that are finely tuned and specific to the individual.

What is the damage that accumulates from not inhibiting NFKB? Can we clean that up without tweaking metabolism?

Edited by caston, 18 May 2008 - 04:19 AM.


#7 niner

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Posted 18 May 2008 - 05:08 AM

Well NFKB inhibition will effect metabolism. Inflammation is a defensive (self offensive) and healing response. While reducing phagoctye numbers may be benefical we are talking a lot of complicated and little understood interconnecting pathways in human metabolism that are finely tuned and specific to the individual.

What is the damage that accumulates from not inhibiting NFKB? Can we clean that up without tweaking metabolism?

Arthritis, asthma, bowel diseases, skin disorders, probably a lot of cardiovascular disease, some cancer, you name it. I would just love to have some good compounds to knock down NFKB. (So would every drug company on the planet- it's kind of a tough nut to crack.) Fixing the damage might be a tougher nut to crack; it would essentially be regenerative medicine. We are going to want to be able to grow immunocompatible lungs and articular cartilage regardless of whether we get an NFKB therapy, so in the end that could be a fix. The value of some of our immune responses is debatable. When I get a certain kind of insect bite, I get a wild immune response with a fair amount of tissue damage, if I don't hit it with massively potent steroids. I guess this is something that was helpful to my distant ancestors, but I could live without it. I have other ways of dealing with parasites and infections.

#8 caston

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Posted 18 May 2008 - 06:02 AM

Well NF-KB inhibition will effect metabolism. Inflammation is a defensive (self offensive) and healing response. While reducing phagoctye numbers may be beneficial we are talking a lot of complicated and little understood interconnecting pathways in human metabolism that are finely tuned and specific to the individual.

What is the damage that accumulates from not inhibiting NF-KB? Can we clean that up without tweaking metabolism?

Arthritis, asthma, bowel diseases, skin disorders, probably a lot of cardiovascular disease, some cancer, you name it. I would just love to have some good compounds to knock down NF-KB. (So would every drug company on the planet- it's kind of a tough nut to crack.) Fixing the damage might be a tougher nut to crack; it would essentially be regenerative medicine. We are going to want to be able to grow immunocompatible lungs and articular cartilage regardless of whether we get an NF-KB therapy, so in the end that could be a fix. The value of some of our immune responses is debatable. When I get a certain kind of insect bite, I get a wild immune response with a fair amount of tissue damage, if I don't hit it with massively potent steroids. I guess this is something that was helpful to my distant ancestors, but I could live without it. I have other ways of dealing with parasites and infections.



There of course are other things we can do help us stop developing these diseases like maintaining healthy diet and exercise, removing chlorine from our water, avoiding irritants. Sure it could turn out that inhibiting NF-KB would be a helpful adaption for modern times and if so some newborns may already have it. I say some but not all because promiscuous sex risks reproductive health (through exposure to foreign pathogens and infection) but without sex there is no reproduction. So in theory the immune response is carefully modulated to protect the reproductive system from disease as much as possible while without destroying it before the host has significant time to reproduce.

I would try to avoid that insect bite because while it is a small event it is not insignificant. What does the insect bite introduce into your body? toxins, viruses, bacteria... etc
The actual complexity of the that event e.g. of the invading bite and the bodies response is enormous at the nanoscale level and you were born because your ancestors weren't killed by that bite.

I'd be careful to emphasis though that independent research into this should not be followed by "using oneself as a guinea pig".

Some of our genes *may* over respond because they are left-overs from harsher times but we can't predict what harshness will come to us in the coming times.

We need to be able to make an informed decision if inhibiting NF-KB (or any attempt to preemptively stop damage be it modifications to diet or supplementation) will allow us to survive long enough until rejuvenation therapies become available and we must be intelligent and light hearted about our decisions not grim and dumb. Social resources tend to be allocated to those that take risks in which the gains come in the form of increased reproduction for both themselves and their financiers.

If we can rejuvenate peoples reproductive systems we won't have to resort to cheaper methods of "life extension" that will be difficult to gain funding for.

NF-KB inhibition may make sex more dangerous and no one wants that.

Of course we are getting off-topic here because we are talking about the appearance of skin from the original poster. Sure NF-KB inhibition may help people have younger looking skin which could help them gain partners that may otherwise be turned off by a wrinked complexion but the overall neuro/muscular/skeletal/cardio youthfulness is what we are after.

Edited by caston, 18 May 2008 - 07:32 AM.


#9 Guest_Kismet_*

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Posted 29 May 2008 - 02:55 PM

 
There of course are other things we can do help us stop developing these diseases like maintaining healthy diet and exercise, removing chlorine from our water, avoiding irritants. Sure it could turn out that inhibiting NF-KB would be a helpful adaption for modern times and if so some newborns may already have it.

Seeing that transgenic mice lacking NF-KB suffer from embryonic lethality it is very probable this would translate to humans.
Why should a longevity gene be naturally selected? I think fitness > longevity when it comes to natural selection.

I say some but not all because promiscuous sex risks reproductive health (through exposure to foreign pathogens and infection) but without sex there is no reproduction. So in theory the immune response is carefully modulated to protect the reproductive system from disease as much as possible while without destroying it before the host has significant time to reproduce.

I would try to avoid that insect bite because while it is a small event it is not insignificant. What does the insect bite introduce into your body? toxins, viruses, bacteria... etc
The actual complexity of the that event e.g. of the invading bite and the bodies response is enormous at the nanoscale level and you were born because your ancestors weren't killed by that bite.

I'd be careful to emphasis though that independent research into this should not be followed by "using oneself as a guinea pig".

Resveratrol suppresses NF-KB to some extent, both topical and systemic application is possible, and recently there was a thread in the resveratrol section about res, NF-KB inhibition and herpes - may be of some interest to you.

We need to be able to make an informed decision if inhibiting NF-KB (or any attempt to preemptively stop damage be it modifications to diet or supplementation) will allow us to survive long enough until rejuvenation therapies become available and we must be intelligent and light hearted about our decisions not grim and dumb. Social resources tend to be allocated to those that take risks in which the gains come in the form of increased reproduction for both themselves and their financiers.

I absolutely agree, who doesn't? Playing guinea pig is never a good idea and as long as we do not completely understand the role of NF-KB there are some risks involved. Though, systemic inhibition is MUCH MORE dangerous than topical inhibition, which was tested in this study and found to be quite save and effective.

If we can rejuvenate peoples reproductive systems we won't have to resort to cheaper methods of "life extension" that will be difficult to gain funding for.

NF-KB inhibition may make sex more dangerous and no one wants that.

Of course we are getting off-topic here because we are talking about the appearance of skin from the original poster. Sure NF-KB inhibition may help people have younger looking skin which could help them gain partners that may otherwise be turned off by a wrinked complexion but the overall neuro/muscular/skeletal/cardio youthfulness is what we are after.

Frankly, I don't have a clue what you are talking about (just wanted to address some misconceptions).. sexuality, danger, reproduction? Is this a pihlosophical debate?
Let us refrain from any further discussion of systemic NF-KB inhibition or sexuality & co and focus on skin aging.

The study outlined that CR works in part by NF-KB inhibition. Very interesting..

May overexpression of NF-KB be one reason why aged skin is chronically inflamed?

Edited by Kismet, 29 May 2008 - 02:57 PM.





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