In the December 15th cover story of G&D, a research team led by Dr. Howard Chang (Stanford University School of Medicine) reports that the blockage of a single gene, called NF-êB, can reverse aging in the mammalian skin. This finding sets the stage for the development of future genetic age-intervention therapies.
Their paper will be published online ahead of print at www.genesdev.org.
“Here we show that aging in mouse skin can be reversed by blocking a single gene... These findings suggest that aging is not just a result of wear and tear, but is also the consequence of a continually active genetic program that might be blocked for improving human health,” states Dr. Chang.
Using large-scale genomic microarray screens, Dr. Chang and colleagues identified NF-êB as a master regulator of aging-associated gene expression programs in humans and mice – effectively demonstrating that an increase in NF-êB target gene expression is a common theme of aging in mammals.
The researchers then used a transgenic mouse model to test the effect of specifically inhibiting NF-êB in the basal layer of the mouse epidermis. Their results showed a striking outcome: After two weeks of NF-êB inhibition, both the global gene expression profile and the tissue characteristics of the aged skin reverted to that of a young animal.
Thus, while NF-êB activity normally increases as mammals age, the targeted blockage of NF-êB in the skin effectively rejuvenates the tissue. “The finding that aged skin can be "rejuvenated" by a genetic intervention late in life implies that the aging program is plastic, and therefore can be potentially manipulated to decrease the deleterious effects of aging,” explains Dr. Chang
Journal
Genes & Development