Interesting new study on muscle and aging

Here's information from an interesting study on muscle growth and aging--some food for thought for those of us over a certain age. The upshot of the article seems to be that, past a certain age, muscle tissue does not grow and/or repair itself. Of course the study indicates that they're working on ways to overcome that limitation.

As you'll see, the older subjects in the study are quite a bit older than this pentagenarian, so the study seems to apply in a limited way to folks my age. I already had some sense of this since I'm certain that since I started my strength training about 1.5 years ago I've gained some muscle. Probably muscle growth rate would have been much more dramatic had I been doing what I'm now doing at, say, age 25.

But it was never and will never be my goal to get anywhere near any body-builder sort of figure. I'm happy with where I'm at in terms of physical form and have begun to cut back a bit on the intensity of my strength training sessions (more reps with lighter weight).

Anyway, without further ado, the article about the study:

Scientists Discover Clues To What Makes Human Muscle Age
Main Category: Seniors / Aging
Also Included In: Biology / Biochemistry; Stem Cell Research; Biology / Biochemistry
Article Date: 01 Oct 2009 - 0:00 PDT

A study led by researchers at the University of California, Berkeley, has identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, the researchers were able to turn back the clock on old human muscle, restoring its ability to repair and rebuild itself.

The findings will be reported in the Sept. 30 issue of the journal EMBO Molecular Medicine, a peer-reviewed, scientific publication of the European Molecular Biology Organization.

"Our study shows that the ability of old human muscle to be maintained and repaired by muscle stem cells can be restored to youthful vigor given the right mix of biochemical signals," said Professor Irina Conboy, a faculty member in the graduate bioengineering program that is run jointly by UC Berkeley and UC San Francisco, and head of the research team conducting the study. "This provides promising new targets for forestalling the debilitating muscle atrophy that accompanies aging, and perhaps other tissue degenerative disorders as well."

Previous research in animal models led by Conboy, who is also an investigator at the Berkeley Stem Cell Center and at the California Institute for Quantitative Biosciences (QB3), revealed that the ability of adult stem cells to do their job of repairing and replacing damaged tissue is governed by the molecular signals they get from surrounding muscle tissue, and that those signals change with age in ways that preclude productive tissue repair.

Those studies have also shown that the regenerative function in old stem cells can be revived given the appropriate biochemical signals. What was not clear until this new study was whether similar rules applied for humans. Unlike humans, laboratory animals are bred to have identical genes and are raised in similar environments, noted Conboy, who received a New Faculty Award from the California Institute of Regenerative Medicine (CIRM) that helped fund this research. Moreover, the typical human lifespan lasts seven to eight decades, while lab mice are reaching the end of their lives by age 2.

Working in collaboration with Dr. Michael Kjaer and his research group at the Institute of Sports Medicine and Centre of Healthy Aging at the University of Copenhagen in Denmark, the UC Berkeley researchers compared samples of muscle tissue from nearly 30 healthy men who participated in an exercise physiology study. The young subjects ranged from age 21 to 24 and averaged 22.6 years of age, while the old study participants averaged 71.3 years, with a span of 68 to 74 years of age.

In experiments conducted by Dr. Charlotte Suetta, a post-doctoral researcher in Kjaer's lab, muscle biopsies were taken from the quadriceps of all the subjects at the beginning of the study. The men then had the leg from which the muscle tissue was taken immobilized in a cast for two weeks to simulate muscle atrophy. After the cast was removed, the study participants exercised with weights to regain muscle mass in their newly freed legs. Additional samples of muscle tissue for each subject were taken at three days and again at four weeks after cast removal, and then sent to UC Berkeley for analysis.

Morgan Carlson and Michael Conboy, researchers at UC Berkeley, found that before the legs were immobilized, the adult stem cells responsible for muscle repair and regeneration were only half as numerous in the old muscle as they were in young tissue. That difference increased even more during the exercise phase, with younger tissue having four times more regenerative cells that were actively repairing worn tissue compared with the old muscle, in which muscle stem cells remained inactive. The researchers also observed that old muscle showed signs of inflammatory response and scar formation during immobility and again four weeks after the cast was removed.

"Two weeks of immobilization only mildly affected young muscle, in terms of tissue maintenance and functionality, whereas old muscle began to atrophy and manifest signs of rapid tissue deterioration," said Carlson, the study's first author and a UC Berkeley post-doctoral scholar funded in part by CIRM. "The old muscle also didn't recover as well with exercise. This emphasizes the importance of older populations staying active because the evidence is that for their muscle, long periods of disuse may irrevocably worsen the stem cells' regenerative environment."

At the same time, the researchers warned that in the elderly, too rigorous an exercise program after immobility may also cause replacement of functional muscle by scarring and inflammation. "It's like a Catch-22," said Conboy.

The researchers further examined the response of the human muscle to biochemical signals. They learned from previous studies that adult muscle stem cells have a receptor called Notch, which triggers growth when activated. Those stem cells also have a receptor for the protein TGF-beta that, when excessively activated, sets off a chain reaction that ultimately inhibits a cell's ability to divide.

The researchers said that aging in mice is associated in part with the progressive decline of Notch and increased levels of TGF-beta, ultimately blocking the stem cells' capacity to effectively rebuild the body.

This study revealed that the same pathways are at play in human muscle, but also showed for the first time that mitogen-activated protein (MAP) kinase was an important positive regulator of Notch activity essential for human muscle repair, and that it was rendered inactive in old tissue. MAP kinase (MAPK) is familiar to developmental biologists since it is an important enzyme for organ formation in such diverse species as nematodes, fruit flies and mice.

For old human muscle, MAPK levels are low, so the Notch pathway is not activated and the stem cells no longer perform their muscle regeneration jobs properly, the researchers said.

When levels of MAPK were experimentally inhibited, young human muscle was no longer able to regenerate. The reverse was true when the researchers cultured old human muscle in a solution where activation of MAPK had been forced. In that case, the regenerative ability of the old muscle was significantly enhanced.

"The fact that this MAPK pathway has been conserved throughout evolution, from worms to flies to humans, shows that it is important," said Conboy. "Now we know that it plays a key role in regulation and aging of human tissue regeneration. In practical terms, we now know that to enhance regeneration of old human muscle and restore tissue health, we can either target the MAPK or the Notch pathways. The ultimate goal, of course, is to move this research toward clinical trials."

Other co-authors of the EMBO Molecular Medicine paper include Abigail Mackey at the University of Copenhagen in Denmark, and Per Aagaard at the University of Southern Denmark.

The National Institutes of Health, the California Institute of Regenerative Medicine, the Danish Medical Research Council and the Glenn Foundation for Medical Research helped support this research.

Source:
Sarah Yang
University of California - Berkeley

Anyone who knows someone that's suffered a major injury--say a bone fracture--after age 40 or so will not be surprised by the results of this study. Those I've known to suffer such injuries at that age or later often never fully recover the strength or flexibility they formerly had in the affected area.

On a final note I need to mention that my shoulder pain is returning now that we've resumed strength training. Were I pressed to point to what's causing it, I think I'd have to say the push-ups. But I do so many different types of exercises when strength training that I'm not sure I can pinpoint the cause without doing some in-depth testing.

Also, I'm beginning to look into Pilates for men. That might be a good supplement and/or alternative, at intervals, to our strength training. More on that in a future entry.

Inspiration for a new winter cycling regimen

I'm usually on the look-out for ways to vary our fitness routine. Why? So that keeping fit won't become something boring, some kind of trudgery. The latest on that front is an article I actually read some time ago (at least 6 months back I'd say).

The original article I read had kind of a gaudy title--something like "stay fit exercising six minutes a week." Despite the snake-oil-salesman sound of it the article was based on a medical study that investigated the effects of interval training. Even more to the point, the subjects in the study rode exercise bikes. So it seemed to offer some promise with respect to my idea of regularly "changing things up" in our routine and a way to possibly cut back healthfully on our regimen for part of the year.

Anyway, without further ado, here's an article similar to the one I read:

Fitness 'takes 6 minutes a week'

Monday, June 6, 2005
Short sprints are more beneficial than long runs, the study says.

LONDON, England -- Six minutes of pure, hard exercise a week could be just as effective as an hour of daily moderate activity, according to a new study.

"Short bouts of very intense exercise improved muscle health and performance comparable to several weeks of traditional endurance training," said Martin Gibala, an associate professor at Canada's McMaster University.

The research, published in the June edition of the Journal of Applied Physiology, says that repeatedly doing very intense exercise such as sprinting resulted in unique changes in skeletal muscle and endurance capacity, similar to training that requires hours of exercise each week.

Sixteen subjects were used in the test: Eight who performed two weeks of sprinting at intervals, and eight who did no exercise training.

The program had in it four and seven 30-second bursts of "all out" cycling followed by four minutes of recovery time, three times a week for two weeks.

Researchers found that endurance capacity in the sprint group increased on average from 26 minutes to 51 minutes, whereas the control group showed no change.

The muscles of the trained group also showed a significant increase in a chemical known as citrate synthase, an enzyme that is indicative of the tissue's power to use oxygen.

"Sprint training may offer an option for individuals who cite lack of time as a major impediment to fitness and conditioning," said Gibala.

"This type of training is very demanding and requires a high level of motivation, however less frequent, higher intensity exercise can indeed lead to improvements in health and fitness."

Extracted from McMaster university journal of Applied physiology, discovered and published by Martin Gibala.

Looks very interesting to me, and very much along the lines of the experiment I wanted to try during cycling off-season anyway. To refresh our memories a bit on that, I wondered, since riding stationary bikes one half hour four days a week seemed to keep us in pretty good cycling form over the winter months, what would be the effect of riding for only fifteen minutes four days a week during part of the cycling off-season?

Well, this article has given me an idea about how to implement that. I think we'll try riding fifteen minutes per session during a certain part of this winter--say, from December through March. But instead of the usual high rpm, steady heart-rate pace we've been keeping on our half hour rides, we'll do intervals. At the moment I'm envisioning thirty-second intervals where we go all out followed by four minutes or so of liesurely riding followed by another thirty-second burst, etc, until the 15 minute period is up.

At this point, I'm still planning exactly how we'll implement this strategy. But it should be something very close to what I've just described. I'm anxious to try it out and see what the effects will be. And you can rest assured that once I determine the particulars I'll report them in this blog--as well as the results at the end of our trial period for this method.

On other related fronts, my shoulder--even after our third strength-training session following our vacation--continues to feel ok. I'm hoping the break from exercise allowed it to fully heal. I'll keep posting here on that topic as well.