FOUNTAIN OF YOUTH: Removal of Two Tissue Inhibitors of Metalloproteinases (TIMP1 & TIMP3) Leads to Rise in Mammary Stem Cell Number and Preserves Youthful Breast Tissue in Aging Mice; No Cancer Increase Observed with Greater Number of Stem Cells

In a study carried out in the mammary glands of genetically modified mice, a research team led by Professor Rama Khokha, Ph.D., of the University of Toronton (U of T) has found that when two factors [TIMP1 (image) and TIMP3] that control tissue development are removed, the normal impact of aging on breast tissue does not occur and the tissue remained youthful in aged mice. Think of tissue as a building that is constantly under renovation. The contractors would be "metalloproteinases," which are constantly working to demolish and reconstruct the tissue. The architects in this case, who are trying to reign in and direct the contractors, are known as "tissue inhibitors of metalloproteinases" -- or TIMPs. When the architect and the contractors don't communicate well, a building can fall down. In the case of tissue, the result can be cancer. To understand how metalloproteinases and TIMPs interact, medical researchers breed mice that have one or more of the four different types of TIMPs removed. Dr. Khokha's team examined the different combinations and found that when TIMP1 and TIMP3 were removed, breast tissue remained youthful in aged mice. The results were published online on February 23, 2015 in Nature Cell Biology. The article is titled “Expansion of Stem Cells Counteracts Age-Related Mammary Regression in Compound Timp1/Timp3 Null Mice.” In the normal course of aging, tissue loses its ability to develop and repair as quickly as it did in youth. That's because stem cells, which are abundant in youth, decline in number with the passing of time. The U of T team found that with the TIMP1 and TIMP3 “architects” missing, the pool of stem cells expanded and remained functional throughout the lifetime of these mice.
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