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Gene Tweak Reverses Aging in Mouse Skin Cells
Date:11/29/2007

It's a long way from this to a human 'fountain of youth,' however

THURSDAY, Nov. 29 (HealthDay News) -- Scientists say they've been able to temporarily return old skin cells to their youthful state by blocking the activity of a single gene.

"This gene gets more and more active with age," said lead researcher Dr. Howard Chang, an assistant professor of dermatology at Stanford University. "It doesn't exist to make us old. It is active in a number of processes, including the immune system and inflammation."

Chang said tweaking the gene, which produces a protein called NF-kappa-B, will not serve as a "fountain of youth" for the foreseeable future. The protein has a number of functions, some involved with cancer, and as-yet-unknown side effects must be explored before its safety is known. But one possible use is to help heal wounds more quickly in older people, he noted.

What's exciting about the discovery is that a single gene can have an immediate effect on older cells, Chang said. "People have known that you can affect the aging process with drastic interventions, like calorie restriction. Now we are talking about a single gene that, if blocked in an individual who is already old, can return cells to a youthful status, at least temporarily."

The researchers came across NF-kappa-B by searching existing data on genes that become more or less active as people get older. They found that the activity of a number of those genes is regulated by the protein.

They then used a genetically engineered mouse model to test the effect of inhibiting NF-kappa-B activity in a patch of skin cells.

After two weeks, a patch of treated skin from a 2-year-old mouse not only had the same genetic activity as that of a newborn animal but also looked more youthful, with more dividing cells.

It's fascinating "to engineer a mouse so that the rest of the mouse is old, but that one patch is young, to see that even locally, in a targeted way, you can affect the aging process," Chang said.

The finding also adds support to the theory that aging is not simply a process of wear-and-tear but the result of specific genetic changes, he said. And it shows that at least locally and temporarily, those changes can be stopped, Chang added.

The gene treatment has to be used cautiously, because NF-kappa-B is involved in so many different processes in the body, he noted.

A question to be asked now is, "What is the long-term effect of blocking the aging process for a while?," Chang said. "Would the tissue age rapidly again after the treatment stopped, or would they take much longer to age? It's important to sort these things out."

Long-term blockage of the gene would raise serious issues in terms of side effects, Chang said, since the gene is involved in so many body processes. Short-term use -- for wound healing, for example -- might sidestep those problems.

More information

There's more on skin aging at the U.S. National Library of Medicine.



SOURCES: Howard Chang, M.D., Ph.D., assistant professor, dermatology, Stanford University, Stanford, Calif; Nov. 29, 2007, Genes and Development


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