Bone and fat: decoding the balancing act of ageing

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Ageing is a complex process that involves every cell in the body and leads to the deterioration of body functions over the lifespan of an individual. Most of this deterioration is linked to our blood vessels. As we age, our tiny blood vessels that supply oxygen and nutrients to our organs, wither and die. This blood vessel damage is responsible for a constellation of human age-related adverse outcomes, such as cardiac and neurologic conditions, muscle loss, and overall frailty. When we are young, aged cells and damaged blood vessels are readily rejuvenated through regeneration. As the regenerative prowess is determined by the ability and potential of our stem cells to replace damaged tissue or aged/worn-out cells, we are as young as our stem cells. Stem cells that are regenerate our blood vessels are mostly found in our long bones. Ageing turns our bones brittle and it takes much longer for bones to heal when fractured. Most importantly, our bones become fatty. The most important fundamental question, therefore, is whether we can restore our blood vessel-forming stem cells if we prevent fatty changes in bones. My research program examines this idea that preserving the integrity of the sites in our body where these stem cells reside will restore their function, effectively `helping the blood vessel repair itself'. To answer the fundamental question posed, I will examine the bones of aged mice and compare the function of blood vessel-forming stem cells to young mice. Next, I will use a cell culture system in which I will grow certain portions of bones in a petri dish to figure out the mechanisms by which fat cells provide harmful signals to the stem cells. I expect that ageing will cause the bones of mice to be fragile and filled with fat, similar to what happens in people over time. I also expect that these changes will cause a drop in the number of blood vessel-forming stem cells. Preventing the bones from fatty changes will prevent bone fragility and restore the number of stem cells to normal levels. I believe that when these mice experience blood vessel damage, their stem cells will be able to combat the changes and repair the damaged vessels. My research will also lead to the discovery of new molecules and processes that keep our stem cells in a stem cell state. My proposed research program will have an impact on several areas. First, understanding of the molecules and processes that enable stem cells to maintain their function and differentiate to rejuvenate damaged blood vessels might be the key to regenerative medicine and an eventual cure for many age-related disorders. Second, my results will provide fundamental knowledge on how bones form, which has implications for osteoporosis. Finally, my studies may generate new knowledge on how to expand stem cells for other stem cell-based applications.