Sean Morrison Discusses Stem Cells and Aging

One of the fundamental characteristics of aging is a decline in tissue regenerative capacity. It just takes longer to heal after injury. Why is that? People tend to think our bodies just don’t work as well when we get older. The real answer is much more interesting.

Studies in my lab and others have shown that stem cell function declines in multiple tissues as we age. Part of the reason is that stem cells shut themselves down by turning on genes known as tumor suppressors. As the name implies, one important function of those genes is to prevent cells from turning into cancer cells.

In mice, when we prevent those genes from turning on, we are able to maintain higher levels of stem cell function during aging and improve regenerative capacity. However, this also causes the mice to develop more cancers, at a younger age. So, stem cells may be shutting themselves down during aging to avoid turning into cancer cells.

The bottom line is that, with aging, stem cells trade lower regenerative capacity for lower cancer risk. Put another way, to reduce the risk of getting cancer as we get older, we have to accept getting older.

We are now trying to more globally understand the mechanisms that regulate temporal changes in stem cell properties throughout life. We know that stem cells in fetal tissues are different from stem cells in young adult tissues, which are different from stem cells in older adult tissues.

During the fetal stage, stem cells divide as rapidly as possible to support tissue growth, but during adulthood they are primarily in maintenance and repair mode. The question we are working to answer is how and why that shift takes place. We have identified regulatory mechanisms that operate only during certain times during the lifespan, conferring stem cell properties appropriate to that stage of life.

This shows that a lot of the changes in tissue growth and regeneration that occur during our lives are genetically programmed obsolescence. Environmental influences further modulate this process. For example, smoking accelerates biomarkers of aging, while exercise slows them.

When we look at patients who have cancer, we find that patients at different ages have a different spectrum of genetic mutations underlying their cancers. Because of what we know about the way different regulatory mechanisms come into play at different stages of life, we know that cancers hijack different mechanisms to promote proliferation at different ages. Taking this into account, additional studies could allow us to better tailor cancer therapies to patient age.

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