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27 March 2011

Phys Ed: More Bone (and Less Fat) Through Exercise

For those requiring additional reasons to show up at the running path or at the gym in the dreary heart of winter, science has come up with a compelling new motivation. Exercise can, it appears, keep your bone marrow from becoming too flabby.
This idea is the focus of a series of intriguing recent experiments by Janet Rubin, a professor of medicine at the University of North Carolina and other researchers. For the work, scientists removed bone marrow cells from mice and cultured them. The cells in question, mesenchymal stem cells, are found in bone marrow in both animals and people, waiting for certain molecular signals to tell them to transform into either bone cells, fat cells or, less commonly, something else.
After a stem cell differentiates, of course, it can no longer be anything else: once a fat cell, always a fat cell; once a bone cell, etc. So the fate of marrow stem cells determines the strength and quality of the bone. If a stem cell becomes a fat cell, then the portion of the skeleton to which it might have migrated as a bone cell will be that littlest bit punier. In a study published late last year by researchers at the University of Southern California, the femurs of healthy adults, some in their 20s, others past age 55, were scanned with magnetic resonance imaging. The researchers found that, in both young and old, the amount of fat in the leg’s bone marrow was inversely related to the amount of bone. The more fat in the marrow, the less bone in the thigh.
But what drives a particular stem cell to become a fat cell instead of a bone cell, and does exercise play a role? Earlier experiments by Clinton Rubin, Janet Rubin’s brother and the director of the Center for Biotechnology at Stony Brook University, had shown that mice placed on platforms that were gently vibrating — in an approximation of the forces generated by the muscular contractions of a gentle stroll — developed more bone density than mice who just sat around. Closer examination of the marrow in these experimental mice found that specific genes and gene transcription factors had been stimulated by the vibrations and had, in turn, directed the stem cells to transform into bone.
Something similar happened when Janet Rubin worked directly with the stem cells themselves, even though she was setting them up to become fat cells. To that end, she and her colleagues bathed them in what she calls “a sweet soup,” a medium infused with extra insulin and other elements that normally would encourage the stem cells to differentiate into fat. “They love to become fat cells,” Dr. Rubin said. “It’s discouragingly easy to nudge them in that direction.”
But when the mesenchymal stem cells were stimulated with mechanical vibrations, when they were, in effect, exercised, they did not all become fat cells. “There was a really striking difference in outcomes,” Dr. Rubin said. Her earlier studies with high-magnitude mechanical signals closely approximated a brisk cellular jog. Now she applied lower-magnitude vibrations twice a day, with a rest period of several hours in between. Once again, the stem cells did not all differentiate into fat, even though their cell medium was highly fat-inducing. Dr. Rubin suspects that complicated issues of biochemical signaling underlay the stem cells’ response to the dual-dose regimen. She is currently completing experiments she says she hopes will clarify the mechanisms involved.
Already, though, the findings would appear to have compelling, real-world implications. If you don’t want fatty bone marrow and unhealthy bones, Dr. Rubin said, consider breaking up moderate-intensity workouts into several sessions interspersed throughout the day. Dr. Rubin herself often now works out twice a day for 30 minutes, rather than, as she once did, for a single hourlong bout. “This is the first time in my career that something I’ve done in the lab has changed how I exercise,” she said.
Many questions remain, of course. It’s not clear, for one, whether fat cells generated in bone marrow remain in the marrow or move around to pad, say, the thighs. It’s also not known how exercise affects stem cells located outside the bone marrow. Can it prevent the birth of fat cells all over the body? In Clinton Rubin’s experiments with mice, the vibrated animals wound up with less overall body fat than the control mice, but the reasons are unknown.
Still, one lesson is indisputable. Don’t sit still more than you need to, Dr. Rubin said, and don’t let your children loll about either. “One of the concerns raised” by these experiments, she said, “is that if you make fat cells when you’re young, then you’ve lost any opportunity to have that particular cell be bone,” and the fat cell will remain just that, for life.

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