Posted May 18, 2011
Malnutrition and bone loss in the elderly are common problems. A research group based at Georgia Health Sciences University aims to show the two are more closely related than previously known, and that could lead to ways to enhance mechanisms of bone building that might aid in injury repair.
After about six years of putting together applications and building collaborations, the Augusta group landed a prestigious Program Project grant from the National Institutes of Health to study nutrition in bone loss.
The five-year, $6.3 million grant will also fund core facilities in bone biology and adult-derived stem cells that can aid other researchers on campus, said Dr. Mark Hamrick, the interim vice president for research and one of the investigators on the grant. v adults and can happen for a number of reasons, including purchasing power declining over time, making higher-quality, more expensive foods such as fruit, vegetables and meat less affordable, said Dr. Carlos Isales, the program director. And that can affect crucial bone marrow stem cells, he said.
“A lot of these stem cells and cells that help repair the bone after damage require those high-quality nutrients to repair themselves on a daily basis,” Isales said. “And when they are absent, then that predisposes (the elderly) to bone loss and fractures.”
Much of the damage from aging could be due to the loss of stem cell repair, he said.
“If you look at the big picture, you should never age as long as your stem cells are able to reproduce and repair,” Isales said. “So something is changing in the environment to affect the stem cells.”
That disruption might be occurring in the microenvironment around the stem cells, and the group is focused in on a signal called stromal derived factor-1 or SDF-1, said David Hill, a research physiologist at GHSU and the Charlie Norwood VA Medical Center.
“There’s a homing signal to stay in the bone marrow and also encourage these cells to stay on the course to become osteoblasts (bone-building cells) versus becoming possibly fat cells,” he said. “If the signal is lost or, we actually think that it may be forming an antagonist signal, then you’re going to end up losing these cells.”
Interestingly, when they follow the bone marrow stromal cells, they also go to other places of injury in the body, such as to heart muscle after a heart attack and to the brain after a stroke, Hill said.
Maintaining the proper cell signaling is “not only a critical thing for bone formation, but these cells are probably also involved in injury repair mechanisms throughout the body,” he said.
In addition to looking at how nutrition affects these cells and how they are signaled, the group will also be looking at leptin, a hormone that signals to the brain you are full. Leptin sensitivity was thought to fade with aging, so the group suspected that when older mice were injected with it not much would happen, Hamrick said. Instead, those mice decreased body fat and gained bone, which became part of the preliminary data to help secure the grant, he said.
Leptin also appears to regulate the cell SDF-1, Hill said. Leptin caused a stir in the ’90s when it was looked at as a potential weight loss drug but proved not to be that effective. But it also might be easier to administer to humans because it does not suppress appetite in people as much as it does in mice, Isales said.
“It is more acceptable as a therapy in humans,” he said.
In addition to the basic researchers, the program is benefiting from strong collaboration with clinicians, including dentists and orthopedic surgeons.
For instance, the group has gotten the bone marrow from knee replacements done in the clinic and now has about 60 samples to study, from patients ranging in age from teenagers to 90 years old, Hamrick said.
“So we can then look at a lot of the age-related changes in these factors” in those samples, he said.
The group is hoping to go beyond that in human studies, Hill said.
“A lot of the things we see in the mice we’re now trying to get funding for to look at in humans,” he said. “So some of the signaling environments that I think are important in terms of the stem cells we’re now going to start looking at in patient populations.”
And sooner rather than later, end up in the clinic and perhaps even beyond, Isales said. The hope is to find the nutrients that influence the stem cells and help to maintain them, he said.
“Potentially we could at least supplement those,” Isales said. “And make sure that in settings like the hospital or in settings like food services for the elderly that (those nutrients) are viewed more like an essential vitamin than just simply food.”
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Copyright © 2011, The Augusta Chronicle, Ga.
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