Protein linking exercise to bigger, stronger muscles discovered; Finding might lead to new therapies for muscle-wasting diseases

Dec. 6, 2012 — Scientists at Dana-Farber Cancer Institute have isolated a previously unknown protein in muscles that spurs their growth and increased power following resistance exercise. They suggest that artificially raising the protein's levels might someday help prevent muscle loss caused by cancer, prolonged inactivity in hospital patients, and aging.

Mice given extra doses of the protein gained muscle mass and strength, and rodents with cancer were much less affected by cachexia, the loss of muscle that often occurs in cancer patients, according to the report in the Dec. 7 issue of the journal Cell.

"This is basic science at present," commented Jorge Ruas, PhD, first author of the report. "But if you could find a way to elevate levels of this protein, that would be very exciting. For example, you might be able to reduce muscle wasting in patients in intensive care units whose muscles atrophy because of prolonged bed rest." Other applications, he said, might be in disorders such as muscular dystrophy and the gradual loss of muscle mass from aging.

Bruce Spiegelman, PhD, the senior author, led the Dana-Farber team that identified the protein, PGC-1 alpha-4, in skeletal muscle and said it is present in mice and humans. Resistance exercise, such as weight lifting, causes a rise in PGC-1 alpha-4, which in turn triggers biochemical changes that make muscles larger and more powerful, said the researchers.

The protein is an isoform, or slight variant, of PGC-1 alpha, an important regulatory of body metabolism that is turned on by forms of exercise, such as running, that increase muscular endurance rather than size. "It's pretty amazing that two proteins made by a single gene regulate the effects of both types of exercise," commented Spiegelman.

The researchers found that the new protein controls the activity of two previously known molecular pathways involved in muscle growth. A rise in PGC-1 alpha-4 with exercise increases activity of a protein called IGF1 (insulin-like growth factor 1), which facilitates muscle growth. At the same time, PGC-1 alpha-4 also represses another protein, myostatin, which normally restricts muscle growth. In effect, PGC-1 alpha-4 presses the accelerator and removes the brake to enable exercised muscles to gain mass and strength.

"All of our muscles have both positive and negative influences on growth," Spiegelman explained. "This protein (PGC-1 alpha-4) turns down myostatin and turns up IGF1."

Several experiments demonstrated the muscle-enhancing effects of the novel protein. The investigators used virus carriers to insert PGC-1 alpha-4 into the leg muscle of mice and found that within several days their muscle fibers were 60 percent bigger compared to untreated mice. They also engineered mice to have more PGC-1 alpha-4 in their muscles than normal mice who were not exercising. Tests showed that the treated mice were 20 percent stronger and more resistant to fatigue than the controls; in addition, they were leaner than their normal counterparts.

Mice engineered to have extra PGC-1 alpha-4 showed "dramatic resistance" to cancer-related muscle wasting, the scientists found. The mice lost only 10 percent mass in a leg muscle compared to a 29 percent loss in mice with cancer that did not have additional PGC-1 alpha-4, according to the report. The altered mice were also stronger and more active than the normal mice.

Ruas, the first author, is now in the faculty at the Karolinska Institute in Sweden. Other authors are from Dana-Farber Cancer Institute, Harvard Medical School, the University of Colorado, the University of Virginia, and the Mayo Clinic.

The research was supported by NIH grant DK061562 and a grant from Novartis.

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Jorge L. Ruas, James P. White, Rajesh R. Rao, Sandra Kleiner, Kevin T. Brannan, Brooke C. Harrison, Nicholas P. Greene, Jun Wu, Jennifer L. Estall, Brian A. Irving, Ian R. Lanza, Kyle A. Rasbach, Mitsuharu Okutsu, K. Sreekumaran Nair, Zhen Yan, Leslie A. Leinwand, Bruce M. Spiegelman. A PGC-1a Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy. Cell, 2012; 151 (6): 1319 DOI: 10.1016/j.cell.2012.10.050

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Steroid injection linked with significant bone loss in postmenopausal women treated for back pain

Dec. 1, 2012 — Postmenopausal women suffered significant bone density loss in their hip after they were treated with an epidural steroid injection for back pain relief, according to a Henry Ford Hospital study

Bone density loss after six months was six times greater when compared to the typical bone density loss seen in a year in a postmenopausal woman who doesn't receive steroid injection, researchers say.

Shlomo Mandel, M.D., a Henry Ford orthopedic physician and the study's lead author, says physicians should exercise caution prescribing an epidural steroid for select patients, suggesting that multiple injections may compromise bone strength.

"The findings of our study suggest that epidural steroid injections for back pain relief should be approached cautiously in patients at risk for bone fragility," Dr. Mandel says. "Physicians who do prescribe them should consider measures that optimize bone health such as calcium and vitamin D supplements and exercise as part of their patient's treatment plan.

The study will be published in the Dec. 1 edition of Spine.

Back pain is one of the most common medical conditions in the United States, affecting 8 out of 10 people at some point during their lives. As people age, their spine ages with them, causing degenerative changes in the spine.

Patients are typically treated with anti-inflammatory drugs and physical therapy. If symptoms persist, an epidural steroid is often prescribed to alleviate pain and improve function. However, steroid use has been linked to diminished bone quality.

In the observational study, Henry Ford sought to evaluate whether steroid injections used for treating lumbar stenosis, increased the risk of bone loss in postmenopausal women. Lumbar stenosis is an abnormal narrowing of the spine canal. Twenty-eight patients, aged 65 and older and treated between 2007-2010, were evaluated for bone loss using bone density testing and serum biochemical markers prior to receiving an injection, then at three- and six-month intervals.

The bone loss data was compared to bone loss data for postmenopausal women who hadn't been treated with an epidural injection.

"Patients receiving multiple steroid injections with a history of steroid exposure may be especially susceptible to compromised bone strength," Dr. Mandel says.

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Hospital-based exercise programs benefit people with osteoarthritis, study finds

Nov. 10, 2012 — A low-cost exercise program run by Hospital for Special Surgery in New York City has significantly improved pain, function and quality of life in participants with osteoarthritis, according to new research.

The study adds to the growing evidence that exercise is beneficial for osteoarthritis and shows that a hospital-based program can work. The study will be reported at the annual meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP), to be held Nov. 9-14, in Washington D.C.

The new study showed that the weekly exercise programs significantly improved enjoyment of life and balance, and decreased pain and the severity and frequency of falls. "When participants were asked to report their level of pain severity, there were statistically significant reductions in pain from pre- to post-test. Pain is a huge factor in quality of life," said Sandra Goldsmith, director of the Public and Patient Education Department at Hospital for Special Surgery. "If we can offer classes that help to reduce pain, that is a good thing."

Roughly ten years ago, HSS launched its Osteoarthritis Wellness Initiative, which has grown to encompass both an educational component, including lectures and workshops, as well as exercise classes. In the study to be presented at the recent ACR/ARHP meeting, Special Surgery researchers evaluated the effectiveness of the exercise programs on 200 participants.

The classes, which met weekly throughout the year, included Tai Chi, yoga, mat and chair pilates, yoga-lates and dance fitness. Instructors who could tailor exercises for those with osteoarthritis and other musculoskeletal issues supervised the exercise programs. The researchers analyzed results from surveys that were administered before and after the exercise programs. The surveys included measures of self-reported pain, balance, falls and level of physical activity. An 11-point numeric pain intensity scale was used to quantify intensity of muscle or joint pain. The 10-point Brief Pain Inventory was used to measure pain interference on aspects of quality of life, including general activity, mood, walking ability, sleep, normal work (both outside the home and housework), and enjoyment of life.

In the sample of 200 participants, roughly 53% indicated that they experienced pain relief as a result of participating in the exercise programs. In fact, when researchers analyzed the subset of 66 participants who completed both pre and post surveys, a larger proportion, 62%, indicated they experienced pain relief after participating in the exercise programs. The level of pain intensity that participants experienced also significantly dropped from 4.5 to 2.7 in this group, where 0 was no pain and 10 was the worst pain imaginable. When researchers compared participants' estimation of how much pain interfered with various aspects of an individual's life, they identified a 54% improvement in general activity, mood, walking ability, sleep, normal work, and enjoyment of life.

"We asked participants to rate their balance, and we found a statistically significant increase in those who rated their balance as excellent, very good or good, from pre- to post-intervention, " said Dana Friedman, MPH, outcomes manager in the HSS Public and Patient Education Department. Fewer respondents reported falling from pre- to post-test (14.5% vs. 13.1%), as well as sustaining injuries that required hospitalization (12.1% vs. 10.6%).

Linda Russell, M.D., a rheumatologist at HSS who is chair of the Public and Patient Education Advisory Committee, points out that the classes are low cost for patients and the fees cover the majority of costs associated with offering these types of programs, including salaries for the instructors. "We like to get all of our patients involved in exercise, and if we can help with a low-cost alternative to exercising in New York City, because gyms are expensive, then it is wonderful," said Dr. Russell. "Patients benefit from supervised exercise programs with regard to their overall sense of well-being and pain due to their arthritis. We encourage other institutions to launch these types of program."

"We'd like to be a role model for other hospitals, showing them that offering this type of program can help their patients reduce pain and improve quality of life," said Ms. Goldsmith. "We are willing to discuss the details about how to start these programs."

All exercise programs were run through the HSS Public and Patient Education Department, which includes the Greenberg Academy for Successful Aging, a collaborative program between the HSS Public and Patient Education Department and NewYork-Presbyterian Hospital's Irving Sherwood Wright Center for the Aging.

Osteoarthritis is the leading cause of disability in the United States. According to the Centers for Disease Control and Prevention, an estimated 50 million U.S. adults, 22% of the population, suffered from osteoarthritis in 2009, compared with 46 million in 2003-2005. Arthritis affected the daily activities of 21 million adults in 2009. Body mass index influences the prevalence of arthritis; 29.6% of obese adults have arthritis.

Other Hospital for Special Surgery authors involved in the study include Linda Roberts, LCSW, Dana Sperber and Laura Robbins, DSW.

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Targeted micro-bubbles detect artery inflammation: Procedure done in pigs could potentially detect heart disease early in humans

Dec. 12, 2012 — Heart disease is a leading cause of death throughout the world. Doctors say that it is important to detect heart disease early before it becomes too serious. Now, researchers at the University of Missouri have found a way that they believe could help detect heart disease before it progresses too far as well as identify patients who are at risk for strokes.

In a study published in Medicine and Science in Sports and Exercise, Isabelle Masseau, an assistant teaching professor in the MU College of Veterinary Medicine, found that she could use targeted micro-bubbles to detect artery inflammation in pigs. She says that this procedure may help detect patients with heart disease or who are at risk for strokes before those ailments become too serious by monitoring artery inflammation, as that is an early warning sign of health problems. She says this procedure may also help monitor the effectiveness of artery inflammation treatments.

"It can be very difficult to detect early signs of heart disease, especially without the use of invasive procedures," Masseau said. "Doctors often have to wait until serious symptoms occur, such as chest pain or heart attacks, before they are aware of a problem, and many times that is too late. Targeted micro-bubbles have the potential to be able to detect early signs of heart disease very non-invasively."

Early signs of heart disease include inflammation on the insides of arteries, which leads to plaque buildup that could eventually result in heart attacks. Masseau was able to attach specific antibodies to tiny bubbles and then inject those bubbles into pigs with heart disease. The antibodies were able to seek out the inflammation in the pigs' arteries and attach themselves, along with the micro-bubbles, to the inflammatory sites. Then, using an ultrasound machine, Masseau was able to detect the targeted micro-bubbles that had gathered in the arteries of pigs. She says this is the first time the procedure has been successful in large animals.

"Because this procedure was successful in pigs, it also could potentially be reproduced in humans as well," Masseau said. "While it would still be a few years away, injecting targeted micro-bubbles into a human and then scanning them with an ultrasound would be a very simple procedure and could potentially help save lives."

Another part of Masseau's research involved studying pigs to observe the effects exercise has on artery inflammation. Before Masseau detected inflammation in the pigs using the targeted micro-bubbles, she submitted them to cardio exercise and measured its effect. Surprisingly, the exercise did not have any effect on reducing the arterial inflammation; however Masseau says that this does not mean that exercise is not important for heart health.

Masseau was joined in this study by Doug Bowles, a professor in the department of biomedical sciences in the MU Dalton Cardiovascular Research Center, and Michael Davis, a professor and associate head of the department of medical pharmacology and physiology in the MU Dalton Cardiovascular Research Center. The early-stage results of this research are promising. If additional studies, including animal studies, are successful within the next few years, MU officials will request authority from the federal government to begin human trials. After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for heart disease.

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Regular physical activity reduces risk of dementia in older people

Nov. 1, 2012 — Regular physical activity may help older people reduce their chances of getting dementia.

In a new study published in the American Heart Association journal Stroke, older, non-disabled people who regularly engaged in physical activity reduced their risk of vascular-related dementia by 40 percent and cognitive impairment of any etiology by 60 percent.

The protective effect of regular physical activity remained regardless of age, education, changes in the brain's white matter and even previous history of stroke or diabetes, researchers said.

The findings are based on a prospective multinational European study that included yearly comprehensive cognitive assessments for three years. The results are part of increasing evidence that regular physical activity promotes brain health, researchers said.

"We strongly suggest physical activity of moderate intensity at least 30 minutes three times a week to prevent cognitive impairment," said Ana Verdelho, M.D., lead author of the study and a neuroscience researcher at the University of Lisbon, Santa Maria Hospital in Portugal. "This is particularly important for people with vascular risk factors such as hypertension, stroke or diabetes."

The analysis included 639 people in their 60s and 70s; 55 percent were women and almost 64 percent said they were active at least 30 minutes a day three times a week. The activity included gym classes, walking and biking.

The American Heart Association recommends at least 150 minutes of moderate exercise every week or 75 minutes of vigorous exercise for optimal health.

Researchers performed magnetic resonance imaging (MRI) tests at the beginning and end of the study to gauge white matter changes in the brain, an indicator of possible cognitive decline.

"Damage of the cerebral white matter is implicated in cognitive problems including depression, walking difficulties and urinary complaints," Verdelho said. "White matter changes are very common in older people and mainly associated with vascular risk factors like hypertension and stroke."

Throughout the study, researchers asked participants in phone interviews and clinical visits about depression, quality of life and performing everyday activities.

At the end of the follow-up, 90 patients had dementia, including 54 with vascular dementia in which impaired blood flow to the brain causes cognitive decline, and 34 patients met criteria for Alzheimer's disease. Another 147 patients developed cognitive impairment, but not dementia.

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Ana Verdelho et al. Physical Activity Prevents Progression for Cognitive Impairment and Vascular Dementia Results From the LADIS (Leukoaraiosis and Disability) Study. Stroke, 2012 DOI: 10.1161/STROKEAHA.112.661793

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Activity tames holiday stress and triggers a chemical response to help you relax

Nov. 20, 2012 — As holiday crunch time fills your schedule, don't give up your exercise.

"When times get crazy, the thing people give up is exercise, and that's the key thing a person needs. When a person is excitable from stress, the burst of energy that you get from exercise can help burn the adrenaline off and calm you down," said Erica Christ, RD, CDE, an exercise physiologist at Greenwich Hospital's Weight Loss & Diabetes Center. "Exercise allows you time to focus, and gives you a sense of mindfulness that makes the other pieces of your life fall into place," added Christ.

Physical activity also stimulates the neurotransmitter dopamine, which has been linked to post-exercise mood improvement more effectively than antidepressant medications.

It's commonly understood that physical activity is an essential part of any overall health plan. For the Center, Erica Christ uses Pilates, a form of exercise that incorporates graceful movement to build flexibility, muscle strength and endurance while supporting the body's core abdominal and lower back area.

"The physical benefit of Pilates goes beyond strengthening the abs, back, shoulders and buttocks. There is also the importance of concentration and mind-body awareness. Plus there are no pressure joints. It's a very safe, very powerful workout," explained Christ.

Being tri-credentialed as an exercise physiologist, registered dietitian and certified diabetes educator, Erica Christ understands the intricate dance that goes on between food, motion and metabolism. She helps clients learn how to fuel their bodies with energy for their specific lifestyle needs.

"The biggest goal is to teach people how to use exercise as a way to de-stress from the outside world. It's the ability to use an hour to turn off the rest of the world and focus on the task at hand. You become empowered while you're doing it, and that empowerment is motivation for overall self-improvement," said Christ.

Holiday Healthy Eating Reminders

1. Don't try to lose weight during the holidays. Maintaining your current weight is more realistic.

2. Create an environment that supports your weight goal. Keep healthy foods in your home.

3. Keep up with a regular exercise routine.

4. Eat when you are hungry. Stop when you are full.

5. Understand why you eat. Is it boredom? Is it just because the food is there? Drink water instead.

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Therapy for stroke patients improved: More mobility due to deafferentation

Nov. 5, 2012 — Painkilling drugs that make many therapies possible are a blessing for patients. Thanks to modern anesthetics, not only can surgical operations be conducted without causing pain, they are also used for various diagnostic procedures. Anesthetics can be very useful in therapies for stroke patients, as psychologists and physicians of the Friedrich Schiller University Jena (Germany) and the University Hospital Jena are now able to demonstrate.

In the Journal of Neuroscience the researchers present the results of their study, showing how a local anesthetic can distinctly improve the motor skills of patients after a stroke.

"Many stroke patients suffer from chronic impairment of the hand or of the complete arm," Professor Dr. Thomas Weiss explains. Together with expert colleagues the psychologist of the department of Biological and Clinical Psychology at Jena University has been working for a number of years on a specialized medical training therapy which clearly enhances the mobility of stroke patients. In the 'Constraint-Induced Movement Therapy' (CIMT) the healthy arm is being restrained in a cuff, while the stroke-affected arm and hand are intensely training fine motor skills. Patients are asked to carry out tasks such as stacking small toy blocks or putting tiny pins into a perforated board. Daily activities like washing one's hand are part of the training. "Nearly every affected person benefits from this training," Weiss's colleague Prof. Dr. Wolfgang Miltner says. The chair of Biological and Clinical Psychology developed the therapy together with American colleagues and refers to the comprehensive study results about the efficiency of the program. "We are happy to carry out this therapy on many patients -- together with our colleagues from the psychology department in the neurological day hospital," the director of the clinic for Neurology, Prof. Dr. Otto Witte, stresses.

In addition, the impact of the exercise therapy could be clearly enhanced when the sensitivity of the affected arm was lowered by an anesthetic, as the interdisciplinary Jena team was able to demonstrate. In their study, the scientists examined 36 patients. Half of the patients had a local anesthetic cream applied on their forearms. Meanwhile the other patient group only received a placebo. Afterwards, both patient groups went into their exercise therapy for a day.

"Unsurprisingly, the motor performance of all patients was strongly enhanced," Prof. Weiss commented on the result. "Beyond that, it became obvious that the patients who received the anesthetic benefited even more than the placebo group," Weiss says. The researchers could show the reason for this effect using magnetoencephalographic imaging (MEG) of the patients. The temporary interruption of nerve impulses from the forearm leads to a decreasing activity in the brain areas processing these impulses. "At the same time neighboring brain cells are activated more strongly," the Jena Psychologist explains. Thus the brain reacts to the missing impulses from the forearm with an increased sensitivity in the hand as the MEG images showed. Consequently the motor performance improves as well. "This process starts within minutes," Thomas Weiss says.

A subsequent study is going to show whether the combination of local anesthetics and therapeutic exercise will improve the mobility of stroke patients in the long term.

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E. Sens, U. Teschner, W. Meissner, C. Preul, R. Huonker, O. W. Witte, W. H. R. Miltner, T. Weiss. Effects of Temporary Functional Deafferentation on the Brain, Sensation, and Behavior of Stroke Patients. Journal of Neuroscience, 2012; 32 (34): 11773 DOI: 10.1523/JNEUROSCI.5912-11.2012

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