November 30, 2007
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.

Share |      Randall Parker, 2007 November 30 12:54 AM  Aging Appearances


Comments
Brett Bellmore said at November 30, 2007 3:36 AM:

I think my mother, who, in her 80's, has skin so down-regulated that she can't use bandaids without it tearing when they're removed, would gladly take the risk. She's not gonna live long enough to die of skin cancer, most likely.

guest said at November 30, 2007 4:58 AM:

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.

I don't buy this. Suppressing the metabolism of all cells in order to combat cancer is exactly the point of chemotherapy. While chemo has a lot of nasty side effects, an extremely aged appearance is not among them.

Munango-Keewati said at November 30, 2007 10:50 AM:

There's no selective advantage to suppressing cancer in old age, after the reproductive years. How would such a mechanism evolve?

Rafal Smigrodzki said at November 30, 2007 11:05 AM:

Quote: Turning down the metabolism of old damaged cells reduces their ability to start dividing uncontrollably.

This is incorrect - most cancers actually have extremely low oxidative metabolism, they are essentially glycolytic, and yet they do divide uncontrollably. Turning down metabolism therefore does not protect from cancer, and may in fact be one of the important steps in oncogenesis, by attenuating the apoptotic activity of mitochondria and thus preventing the cancer cells from committing suicide.

Rafal

Curious said at November 30, 2007 11:13 AM:

Ah Rafal, nice to see you read this Blog... how is your work on protofection comming along?

Rafal Smigrodzki said at November 30, 2007 11:39 AM:

Protofection? I'd get crucified by my boss if said anything specific :)

But yes, we are working hard on it, mainly slogging through scaling up and refining production....slower than we wish for but moving forward.

(Sorry for inadvertently reposting my previous comment)

Rafal

Randall Parker said at December 1, 2007 11:31 AM:

Rafal,

Perhaps I'm being too uncareful in my language. The genetic changes that MF-kappa-B reverse might not be delivering their benefit by slowing down oxidation of sugar. But those genetic changes probably are preventing other risky cellular activity. Otherwise it seems unlikely that so many genes would get their regulation changed in a way that is detrimental to optimal function and so easily reversed by targeting a single compound.

Manila said at May 23, 2008 2:01 AM:

But NF kappa B is required for the activation of the cells requiring in providing immunity to our body like lymphocytes,and such immune responses will not the blocking of it be harmful to our body in case of an infection.

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