Low Buzz May Give Mice Better Bones and Less Fat

Clinton T. Rubin cognizes full well that his recent consequences are surprising — that no 1 have been more than taken aback than he. And he admonishes that it is far too soon to jump to decisions about humans. But still, he says, what if ...

FAT Abdominal scans of two mice demo subcutaneous fat (gray) and visceral fat (red). The vibrated mouse, right, have less of both.

Multimedia

And no wonder, other men of science say. Dr. Rubin, manager of the Center for Biotechnology at the , is reporting that in mice, a simple treatment that makes not affect drugs looks to be directing cells to turn into os instead of .

All he makes is set mice on a platform that bombinates at such as a low frequence that some people cannot even experience it. The mice stand up there for 15 proceedings a day, five years a week. Afterward, they have got 27 percentage less fat than mice that did not stand up on the platform — and correspondingly more than bone.

"I was the greatest sceptic in the world," Dr. Rubin said. "And Iodine sit down here and say, 'This can't possibly be happening.' I experience like the credibleness of my scientific calling is sitting on a razor's border between 'Wow, this is really cool,' and 'These people are nuts.'"

The responses to his work bear out that feeling. While some men of science are enthusiastic, others are skeptical.

The mice may be less fat after standing on the platform, these research workers say, but they are not convinced of the account — that fat forerunner cells are turning into bone.

Even so, the is sufficiently intrigued to look into the consequence in a big clinical trial in aged people, said Joan A. McGowan, a division manager at the National Institute of and Musculoskeletal and Skin Diseases.

Dr. McGowan short letters that Dr. Rubin is a well-thought-of man of science and that her institute have helped wage for his research for the past 20 years, but she makes cautiousness against jumping to conclusions.

"I'd name it provocative," she said of the new result. "It says, 'Keep looking here; this is exciting.' But it is important that we don't oversell this." For now, she added, "it is a cardinal scientific finding."

The narrative of the finding, which was published online and will look in the Nov. Six issue of Proceeding of the National Academy of Sciences, began in 1981 when Dr. Rubin and his co-workers started asking why os is lost in aging and inactivity.

"Bone is ill-famed for 'use it or lose it,'" Dr. Rubin said. "Astronauts lose 2 percentage of their os a month. People lose 2 percentage a decennary after age 35. Then you look at the other side of the equation. Professional lawn tennis participants have got 35 percentage more os in their playing arm. What is it about mechanical signalings that brands 's arm so big?"

At first, he assumed that the consequence came from a forceful impact — the pounding on the leg castanets as a runner's feet hit the land or the blow to the castanets in a lawn tennis player's arm with every work stoppage of the ball. But Dr. Rubin was trained as a biomechanical engineer, and that led him to see other possibilities. Large signalings can actually be counterproductive, he said, adding: "If I shout at you over the phone, you don't hear me better. If I reflect a bright visible light in your eyes, you don't see better."

Over the years, he and his co-workers discovered that high-magnitude signals, like the 1s created by the impact as ft hits pavement, were not the predominant signalings affecting bone. Instead, os responded to signalings that were high in frequence but low in magnitude, more than like a buzzing than a pounding.

That do sense, he went on, because musculuses frisson when they contract, and that quivering is the predominant signaling to bones. It happens when people stand up still, for example, and their musculuses contract to maintain them upright. As people age, they lose many of those postural muscles, making them less able to balance, more than liable to fall and, perhaps, prostrate to loss of bone.

"Bone is bombarded with little, teeny signalings from musculus contractions," Dr. Rubin said.

He discovered that in mice, sheep and turkeys, at least, standing on a level vibrating plate led to os growth. Small surveys in world — children with who could not travel much on their ain and immature women with low os denseness — indicated that the vibes might construct os in people, too.

Dr. Rubin and his co-workers got a patent of invention and formed a company to do the vibrating plates. But they and others admonish that it is not known if standing on them beef ups castanets in humans. Even if it does, no 1 cognizes the right dose. It is possible that even if there is an effect, people might overdose and do their castanets worse instead of better.

Some replies may come up from the federal clinical trial, which will include 200 aged people in assisted living. It is being directed by Dr. Stephen A. Douglas P. Kiel, an research worker and manager of medical research at the Institute for Aging Research at Harvard. The animate being work made him hopeful that the buzzing chopine would have got an consequence on human bones.

"This work is absorbing and very legitimate," Dr. Kiel said.

But then Dr. Rubin reported that the mice were also less fat, which led to the revised programs to look for alterations in organic structure fat as well.

Dr. Rubin states he decided to look at whether vibes impact fat because he cognizes what haps with age: os bone marrow fill ups with fat. In osteoporosis, the castanets make not merely thin; their texture goes lacy, and inside the holes is fat. And a few old age ago, men of science discovered a in os os os marrow that tin bend into either fat or bone, depending on what signalize it receives.

No 1 cognizes why the fat is in os marrow — maybe it supplies energy for failing bone cells, proposes Dr. Clifford J. Rosen, manager of the Pine Tree State Center for Osteoporosis Research and Education. And no 1 cognizes whether human fat cells ever go forth the os bone marrow and take up abode elsewhere.

But Dr. Rubin had an idea. "We thought, Wait a second," he said. "If we are mechanically stimulating cells to constitute bone, what isn't happening? We thought maybe these os primogenitor cells are driving down a determination path. Maybe they are not becoming fat cells."

He paid a visit to Jeffrey E. Pessin, a expert at Stony Brook, and presented his hypothesis. Dr. Pessin laughed uproariously. He "almost kicked me out of his office," as Dr. Rubin set it.

But when Dr. Rubin decided to travel ahead anyway, Dr. Pessin joined in. Their hope was to see a little consequence on organic structure fat after the mice stood on the chopine 15 proceedings a day, 5 years a week, for 15 weeks. Dr. Rubin was stunned by the 27 percentage reduction.

"Talk about your jaw dropping," he said.

Some researchers, though, state there may be other grounds that the mice were less fat.

"It is a very challenging paper," said Claude Bouchard, an fleshiness research worker who is manager of the Pennington Center for Biomedical Research at Pelican State State University. But he wondered whether the mice on the platform were simply burning more than .

"It looks to me," Dr. Bouchard said, "that putting myself in the organic structure of a mouse, if I was on a platform that was vibrating 90 modern times a minute, I would seek to accede to the surface and not be thrown off. I would probably tense my legs a small bit. That is energy expenditure."

Stress may be another factor, he added. Standing on the platform may have got got panicky the mice, and they might have go sick.

Dr. Rudolph L. Leibel, an fleshiness research worker who is co-director of the Noemi Berrie Diabetes Center at , had similar questions.

A platform that looks to be barely vibrating to a human could experience like an temblor to a mouse, Dr. Leibel said, adding, "they could be scared to death," which could impact the survey data.

He also questioned the thought that forerunner cells from os bone marrow could turn into fat cells in the remainder of the body, calling it "a contested and, I would say, wrong notion."

If the mice that stood on the platform became thinner and if they ate as much as mice that did not stand up on the platform (as Dr. Rubin reported), they must be combustion more calories, Dr. Leibel said.

Others are more than hopeful.

"This is very, very cool," said Dr. Toilet B. Buse, a diabetes research worker at the who is president for scientific discipline and medical specialty at the American Diabetes Association. If it turned out to throw for people too, "it would be great for diabetes," he added. He noted that people with were likely not only to be fleshy but also to have got jobs with their bones.

Still, Dr. Buse expects more than unequivocal surveys in humans.

"It is almost too good to be true," he said.