2006 AFAR Research Grant: Identification of Factors Regulating Aging of the Stem Cell Niche

Please give a brief summary of your AFAR research project.
Loss of tissue and organ function is a characteristic of aging, and such changes have been attributed to decreases in stem cell function. Stem cells are the building blocks during development of organisms as varied as plants and humans. In addition, stem cells provide for the maintenance and regeneration of tissues, such as blood and skin, throughout the lifetime of an individual. The ability of stem cells to contribute to these processes depends on their ability to divide and generate both new stem cells (self-renewal) as well as specialized cell types (differentiation). Stem cells lose the potential for continued self-renewal when removed from their normal cellular environment, known as the stem cell "niche," suggesting an essential role for the niche in controlling stem cell behavior. The long-term goals of our research are to understand how stem cells, the stem cell environment and the relationship between the two change during aging.

What problems are you addressing and what specific questions will your research seek to answer?
We have found that a major factor contributing to loss of stem cell function over time is aging of the stem cell microenvironment. Our research has shown that one characteristic of aging of the niche is reduced production of self-renewal signals. In other words, the stem cell niche is less able to support stem cells to maintain tissue homeostasis. Therefore, the goal of this project is to determine why the niche no longer produces self-renewal signals and to identify other changes that occur to the stem cell niche in older individuals.

What aspects of your project are most interesting from a scientific point of view?
The fact that the stem cell niche ages was very surprising, as most studies so far had focused on how stem cells age. Our results suggest that it might be possible to maintain stem cell activity and tissue homeostasis longer by ensuring a healthy, functional stem cell environment.

What are the implications of your research for age-related diseases and disorders?
One of the long-term goals of stem cell research is to facilitate the use of stem cells in tissue replacement therapies, also known as regenerative medicine. Regenerative medicine can be defined as a group of new techniques that rely on replacing diseased or dysfunctional cells with healthy ones. In the future, these new techniques may be applied to a wide range of human disorders, including many types of cancer, diabetes, muscle degeneration and neurological diseases such as Parkinson's Disease.

If the regulation of stem cell behavior changes over time, stem cells taken from older patients for autologous transplants may be more difficult to grow, leading to unique hurdles to the maintenance of tissue stem cells derived from older individuals in culture. In addition, when considering transplantation of stem cells to treat aging-related disorders, it may be necessary to transplant supporting niche cells in addition to stem cells to provide a "younger" niche that may be more capable of sustaining stem cell self-renewal over time.

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