Loss of TIMP1 and TIMP3 Maintains Youthful Stem Cell Activity in Aging Mice

Stem cell activity declines with age, an evolutionary trade-off that reduces the risk of death by cancer at the cost of increasing frailty and a slower death due to failure of tissue maintenance. This is just one of the many contributing factors that together determine the present human life span and the course of failing health for most people. Researchers would like to be able to restore youthful stem cell activity in old people without significantly increasing the risk of cancer, as continued tissue maintenance would greatly reduce the impact of aging and incidence of age-related disease.

At present this line of work is still in the comparatively early stages: much of the research community involved is searching for the signals and mechanisms responsible for stem cell decline, changes in the tissue environment that are most likely reactions to rising levels of cellular and molecular damage produced over the course of aging. Some points of potential intervention have been found in recent years, such as altering levels of GDF-11 to improve stem cell function in aged mice. Here is news of another potential basis for therapies, discovered by chance during cancer research:

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 bred mice that have one or more of the four different types of TIMPs removed. The team examined the different combinations and found that when TIMP1 and TIMP3 were removed, breast tissue remained youthful in aged mice.

In the normal course of aging, your tissue losses its ability to develop and repair as fast as it did when you were young. That's because stem cells, which are abundant in your youth, decline with the passing of time. The 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. "Normally you would see these pools of stem cells, which reach their peak at six months in the mice, start to decline. As a result, the mammary glands start to degenerate, which increases the risk of breast cancer occurring. However, we found that in these particular mice, the stem cells remained consistently high when we measured them at every stage of life." The team also found that despite large number of stem cells, there was no increased risk of cancer. "It's generally assumed that the presence of a large number of stem cells can lead to an increased cancer risk. However, we found these mice had no greater predisposition to cancer." The next step in this research is to understand why this is happening.

Link: http://medicine.utoronto.ca/news/breast-cancer-research-uncovers-fountain-youth