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Skin Patch Gives Ageing Mice A Youthful Glow


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#1 Mind

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Posted 30 November 2007 - 04:31 PM


Skin patch gives ageing mice a youthful glow

#2 speda1

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Posted 01 December 2007 - 12:34 AM

If its about inhibiting NF-kB, I wonder if topical curcumin might work too.

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#3 caston

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Posted 01 December 2007 - 02:27 AM

Chang and his teammates used a technology called microarray analysis to get a picture of which ones of the 20,000 genes in the entire mouse genome are most active in the skin at different ages.


Has such a microarray analysis been done in humans?

Edited by caston, 01 December 2007 - 02:28 AM.


#4 Fredrik

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Posted 01 December 2007 - 01:39 PM

Sorry for being a broken record here, but we already have a topical cream that inhibit NF-Kb. Tretinoin, one of the two only drugs to treat aging skin greatly reduce UV-induced activation of AP-1 and NF-Kb in human skin.

NF-Kb controls the skin degrading enzymes collagenase and elastase. It´s one of several mechanisms which retinoids treats, and even prevents aging skin. The others are stimulation of collagen and skin lightening.

"And tretinoin might do more than simply repair wrinkles: it might also stop them happening in the first place. Voorhees refuses to discuss his findings with journalists, but in his Nature paper he reported how several dozen male and female volunteers received a single, quick mild dose of UV-B—about twice the intensity needed to trigger barely perceptible skin reddening—on their bare buttocks. The researchers then sliced off both the irradiated portions of skin and the adjacent, non-irradiated patches, and compared them. In less than a day after irradiating the buttocks, the levels of three enzymes that degrade collagen and elastin had increased roughly fourfold in the skin samples. Within just 15 minutes, the levels of AP1 and NF-kB, proteins that switch on the genes for those enzymes, had more than doubled. When tretinoin was applied before irradiation, however, the increase in AP-1 and NF-kB, and in the collagen and elastin-chewing enzymes was greatly reduced.
"It's a very interesting result," says Christopher Griffiths, professor of dermatology at the University of Manchester. "It's saying that tretinoin might not just repair photodamage, but actually prevent it in the first place."

The skin researchers suspect that tretinoin, a type of retinoid, causes these molecular changes by seeping into the skin and binding to retinoid receptors in cells that, once activated, have profound effects on gene regulation. The widespread presence in the body of the receptors—they are found in many sites besides the skin—reflects the importance of the naturally occurring retinoids such as vitamin A."

http://www.newscient...-cosmetics.html

Edited by fredrik, 01 December 2007 - 02:11 PM.


#5 Johan

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Posted 01 December 2007 - 04:24 PM

Tretinoin, one of the two only drugs to treat aging skin greatly reduce UV-induced activation of AP-1 and NF-Kb in human skin.


What is the other drug? Tazarotene?

#6 Karomesis

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Posted 01 December 2007 - 04:34 PM

If its about inhibiting NF-kB, I wonder if topical curcumin might work too.


indeed it probably is. I don't understand alot of the mechanisms of action with inhibition of NF-kB but it seems like a conductor gene. i.e. symphony of genes.

#7 Fredrik

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Posted 01 December 2007 - 04:54 PM

Tretinoin, one of the two only drugs to treat aging skin greatly reduce UV-induced activation of AP-1 and NF-Kb in human skin.


What is the other drug? Tazarotene?


Yes, tazarotene (brand name AVAGE and TAZORAC but you can order cheap generic taz online).

#8 tom a

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Posted 01 December 2007 - 06:06 PM

Here's a pretty interesting article describing an apparently new research finding, based on work at Stanford:

Skin ageing 'reversed' in mice

I strongly suggest that people listen to the audio interview on the BBC site of the Stanford scientist leading this research -- there's a lot of interesting further detail there.

And here's an article talking about a connection between resveratrol and the relevant protein, NF-kappa-B:

Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation.

I'd be very interested to hear people's reactions to both articles, and in particular to the possible relation between resveratrol and this effect on the aging of the skin.

Update:

Here's the original scientific article re the effects of NF-kappa B

Motif module map reveals enforcement
of aging by continual NF-kappa B activity

Edited by tom a, 01 December 2007 - 08:31 PM.


#9 VP.

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Posted 01 December 2007 - 08:47 PM

Interesting. I wonder if using DMSO and resveratrol applied cutaneously to aged skin would make a difference locally. If anyone wants to try this don't use it on your face as DMSO causes chronic eye damage. http://en.wikipedia....ethyl_sulfoxide
It's a long shot and my understanding of how resveratrol works is very limited but it seems worth a try. (I'm sure the cosmetics industry has already looked into this)

#10 tom a

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Posted 01 December 2007 - 09:15 PM

I notice that this topic has been moved to the "Skin Health" forum, but, really, if you read the associated paper, it deals with aging of ALL tissues -- skin tissues simply were the first target they happened to investigate.

And since it would at first blush seem that resveratrol might achieve the desired effect on the relevant protein, NF-kappa B, it seems pretty relevant in the supplements forum too.

Of course, I suppose it has to go somewhere.

Edited by tom a, 01 December 2007 - 09:20 PM.


#11 Fredrik

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Posted 01 December 2007 - 09:58 PM

See the current thread on this news article:

http://www.imminst.o...mp;#entry210933

#12 missminni

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Posted 01 December 2007 - 10:03 PM

Interesting. I wonder if using DMSO and resveratrol applied cutaneously to aged skin would make a difference locally. If anyone wants to try this don't use it on your face as DMSO causes chronic eye damage. http://en.wikipedia....ethyl_sulfoxide
It's a long shot and my understanding of how resveratrol works is very limited but it seems worth a try. (I'm sure the cosmetics industry has already looked into this)

I am currently using restreverol and DMSO cutaneously on my inner left arm as a method for
taking resveratrol.
Your suggestion is very timely.
I am almost 62 years old and although my skin is not bad or even typical for my age, I did
notice as of a few months ago the beginning of that thinnish crepe look to the skin around
the inner elbow bend when I bend it from a certain angle. I have only been doing the res/dmso
mix for a few days, but I will keep an eye on it to see if there is any change.
I can use the right arm as a control.
Finally, I am doing something quasi-scientific.
Acutally I just compared them, and I don't know if it is the power of suggestion or what, but the left arm skin looks a bit tighter
than the right.
I'll try to figure out how to photograph it when there is more difference. Right now it's too little a difference to
really notice. Only my super critical eye sees it.
Can somebody tell me if mixing collagen and DMSO and putting it on the skin would be dangerous....I mean getting
collagen in the bloodsteam...is that bad?
Vitamin E? Would that be okay?
The idea of using DMSO for transporting skin enhancing products is very appealing, but I am concerned about
those products getting in the blood stream.
Any ideas?


#13 missminni

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Posted 01 December 2007 - 10:14 PM

See the current thread on this news article:

http://www.imminst.o...mp;#entry210933

hmmm
I just read this.
I use tretinoin cream
or Retina A 0.1%
I've used it on and off for years.
I like it, it agrees with me, but I always felt like it needed to be stronger.
What I have is the strongest available commercially, AFAIK.
You also need a script for it. It's very expensive here. It's much less expensive in Canada, but they still require
a prescription.
Do you think it's potency could be enhanced if I combined it with DMSO?


#14 John Schloendorn

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Posted 01 December 2007 - 11:00 PM

Has such a microarray analysis been done in humans?

The microarray analysis incuded humans. (just the skin patch experiment did not)

#15 Mind

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Posted 01 December 2007 - 11:25 PM

Thanks for your report missminni. Keep us up to date. Always good to hear little experiments people are doing...just be safe.

#16 missminni

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Posted 02 December 2007 - 07:00 AM

Thanks for your report missminni. Keep us up to date. Always good to hear little experiments people are doing...just be safe.


Thanks for your concern.
It seems I overdid the DMSO today, and ended up with a couple of severe
nosebleeds. I used to get nosebleeds quite regularly, but when I began
hi dose Resveratrol, they stopped. I gather that DMSO is an anti-coagulant,
so if you already have an issue such as nose bleeding, use it sparingly.


#17 ilanso

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Posted 02 December 2007 - 07:36 AM

missminni: I can use the right arm as a control.

Just a thought (theory): it seems the right brain hemisphere (at least for righties) is subject to a greater age-related decline than the left. Since it mostly controls the organs on the opposite side of the body, I would expect (came to me in a dream) slightly more accumulated age damage (eg more / deeper wrinkles) on the left side. On the outside chance this proves true, you may want to use as control the upper half of the right forearm and the lower left, while smearing the stuff on the lower right and upper left.
And, if possible, temporarily suspend your belief system :wink:

#18 VP.

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Posted 02 December 2007 - 08:15 AM

The idea of using DMSO for transporting skin enhancing products is very appealing, but I am concerned about
those products getting in the blood stream.
Any ideas?


The always excellent Futurepundit Blog has some comments about using drugs to suppress NF-kappa-B:

Suppression Of NF-kappa-B Makes Old Mice Look Younger
What, a way to look younger? Suddenly many readers are paying more attention.

STANFORD, Calif. - Researchers at the Stanford University School of Medicine have reversed the effects of aging on the skin of mice, at least for a short period, by blocking the action of a single critical protein.

The work could one day be useful in helping older people heal from an injury as quickly as they did when they were younger, said senior author Howard Chang, MD, PhD, assistant professor of dermatology. However, Chang and his colleagues warned their finding will likely be useful in short-term therapies in older people but not as a potential fountain of youth.

Imagine the size of the market if this could be done safely. Even a risky way to do this would have a big market if regulatory agencies allowed drugs for restoring youthful appearances to be sold with known publicized risks.

NF-kappa-B regulates gene expression. Gene expression changes as we get older. Suppression of NF-kappa-B restored a more youthful pattern of gene expression and made mice look younger.

Chang said people had long known that NF-kappa-B winds its way into a cell's nucleus to control which genes were active. What they didn't know is that many of those genes regulated by the protein have a role in aging.

Chang and Adler tested whether blocking the activity of NF-kappa-B in the skin of older mice for two weeks had a youthful effect. "We found a pretty striking reversal to that of the young skin," Chang said.

First they looked at the genetic changes resulting from blocking NF-kappa-B. After two weeks, the skin of 2-year-old mice had the same genes active as cells in the skin of newborn mice-a striking difference when compared with the skin of a normal 2-year-old mouse. The skin looked more youthful too. It was thicker and more cells appeared to be dividing, much like the skin of a younger mouse.

Sounds great. So why not just develop drugs that suppress NF-kappa-B and slather them on our faces? We'd run the risk of getting cancer.
Chang and Adler caution that their findings aren't likely to be the source of the long-sought fountain of youth. That's because they don't know if the rejuvenating effects of NF-kappa-B are long-lasting. Also, the protein has roles in cancer, the immune system and a range of other functions throughout the body. Suppressing the protein on a long-term basis could very well result in cancers or other diseases that undermine its otherwise youthful effect.
Effective non-toxic cures for cancer would enable the use of many rejuvenation therapies. Lots of mechanisms by which cells become less active as we age are probably anti-cancer defenses. Turning down the metabolism of old damaged cells reduces their ability to start dividing uncontrollably. Only a very very small fraction of all old cells have accumulated the right set of mutations needed to start a cancer. But the body has to suppress a much larger number of cells in order to make sure the smaller number which are near cancerous won't develop into fully cancerous cells.

Another possibility: Gene therapies will some day repair cells that have mutations that increase the risk of cancer. Then drugs that suppress NF-kappa-B could be applied to the skin without risk of cancer.

By Randall Parker at 2007 November 30 12:54 AM Aging Appearances | TrackBack


http://www.futurepun...ves/004828.html




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