Mechanobiology of aged stem cells: A foundation for improved musculoskeletal healing in the elderly

Funding Type: 
Basic Biology III
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

We focus on how aging affects the function of stem cells in bone. Bone arises from mesenchymal stem cells found within the bone marrow cavity. Many growth factors have been identified that stimulate mesenchymal stem cells to mature into bone-producing cells, but physical signals also have a role in directing mesenchymal cell fate.

Mechanical signals stimulate bone formation and inhibit fat formation, and they do so by acting on mesenchymal stem cells. Aging disrupts this balance, however: aged mesenchymal stem cells have an altered, or blunted, response to the same mechanical stimuli that induce young stem cells to mature into bone-producing cells. This is one reason why, as we age, we tend to lose both the quantity and quality of bone.

Our project is focused on understanding how aging affects the ability of stem cells to sense the mechanical environment around it. This area of study has received limited attention despite the fact that most real-life medical problems are centered on the elderly patient. Our project has broad objectives and requires expertise in many specialities including stem cell biology, bioengineering, animal models of wound healing, and computational methods. By forming an international team we have amassed the kind of expertise that is required to carry out the proposed study. At its conclusion, we envision that results from our collaborative study will establish the foundation for revitalizing aged mesenchymal stem cells and therefore maintaining skeletal health well into old age.

Statement of Benefit to California: 

Every six seconds someone in America sustains a musculoskeletal injury. In young, healthy people the course of skeletal healing is largely unremarkable- save for its extraordinary vigor. But when older individuals or those with diminished healing capacity sustain skeletal damage, then the course of repair is oftentimes complicated. Injuries are not the only problem: diseases that jeopardize or weaken skeletal function constitute the most prevalent chronic impairment in the U.S. and are an increasing concern in less developed regions of the world as well.

Despite the magnitude of the problem, the impact of musculoskeletal diseases on human health is under-appreciated. In part, it is an issue of morbidity versus mortality: musculoskeletal conditions are rarely fatal. Instead, they compromise quality of life and diminish ones capacity to function.

There is a second factor: musculoskeletal diseases are associated with aging. While no one likes to think of themselves as getting old, the undeniable fact is that these chronic conditions translate into a biomedical burden of epic proportions: almost 8% of the U.S. gross domestic product is spent treating musculoskeletal conditions.

In comparison to other parts of the country, California has a young population. Nonetheless, estimates are that by the year 2030, almost 18% of Californians will be over age 65. This aging population, and the fact that people are living longer and expecting to enjoy better fitness and health than previous generations, represents a biomedical challenge to us. We focus on how aging affects the function of our stem cells in bone, but these studies also provide critical insights into how stem cells in other tissues may be affected by growing old. We envision that results from our collaborative study will establish the foundation for therapeutic strategies to revitalize aged stem cells to help maintain skeletal health well into old age.