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New clues to how muscle wasting occurs in people with cancer

Significant muscle wasting — or “cachexia” — occurs in about 80% of people with cancer and is responsible for about 30% of cancer deaths. It’s also associated with a reduced quality of life, problems tolerating chemotherapy and lower survival rates.

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Muscle wasting, or the loss of muscle tissue, is a common problem for people with cancer, but the precise mechanisms have long eluded doctors and scientists. Now, a new study led by Penn State researchers gives new clues to how muscle wasting happens on a cellular level.

Using a mouse model of ovarian cancer, the researchers found that cancer progression led to fewer skeletal muscle ribosomes — particles in the cell that make proteins. Because muscle mass is mainly determined by protein synthesis, having less ribosomes likely explains why muscles waste away in cancer.

Gustavo Nader, associate professor of kinesiology and physiology at Penn State, said the findings suggest a mechanism for muscle wasting that could be relevant not just for people with cancer, but other conditions as well.

“Loss of muscle mass is also associated with the aging process, malnutrition, and people with COVID-19 and HIV-AIDS, among others,” Nader said. “Not only is muscle wasting a common problem, but there’s currently no cure or treatment, either. But now that we understand the mechanism better, we can move forward with trying to find ways to reverse that mechanism.”

According to the researchers, significant muscle wasting — or “cachexia” — occurs in about 80% of people with cancer and is responsible for about 30% of cancer deaths. It’s also associated with a reduced quality of life, problems tolerating chemotherapy and lower survival rates. According to Nader, “cachexia is often the killer, not the tumor.”

Nader said that because there is no current cure or treatment for cachexia, it is vital for scientists to understand precisely how and why it happens. But while there has been a lot of research trying to understand and prevent the mechanism that causes muscles to waste, Nader and his team wanted to tackle the problem from a new angle.

“Most of the focus has been on protein degradation, where people have tried to block proteins from being chopped up, or degraded, in order to prevent the loss of muscle mass,” Nader said. “But many of those efforts have failed, and one reason may be because people forgot about the protein synthesis aspect of it, which is the process of creating new proteins. That’s what we tackled in this study.”

For the study, the team used a pre-clinical mouse model of ovarian cancer with significant muscle loss. By using mice, the researchers were able to study the progression of cancer cachexia over time which would be difficult to do with human patients.

After analyzing their results, the researchers found that mice with tumors experienced a rapid loss of muscle mass and a dramatic reduction in the ability to synthesize new proteins, which can be explained by a drop in the amount of ribosomes in their muscles.

“So we cracked the first layer of this problem, because we showed that there are less ribosomes and less protein synthesis,” Nader said.

Then, the researchers set out to explain why the number of ribosomes was decreased. After examining the ribosomal genes, they found that once a tumor was present, the expression of the ribosomal genes started to decrease until it reached a level that made it impossible for the muscles to produce enough ribosomes to maintain enough protein synthesis to prevent muscle loss.

Nader said that while more research is needed, he hopes the findings — recently published in the Federation of American Societies for Experimental Biology Journal — can eventually contribute to prevent people from losing muscle mass and function.

“If we can better understand how muscles make ribosomes, we will be able to find new treatments to both stimulate muscle growth and prevent muscle wasting,” Nader said. “This is especially important considering that current approaches to block tumor progression target the ribosomal production machinery, and because these drugs are given systemically, they will likely affect all tissues in the body and will also impair muscle building.”

Hyo-Gun Kim, Penn State; Joshua R. Huot, Indiana University School of Medicine; Fabrizio Pin, Indiana University School of Medicine; Bin Guo, Penn State; and Andrea Bonetto, Indiana University School of Medicine, also participated in this work.

Fitness

Study finds moderate-vigorous physical activity is the most efficient at improving fitness

Dedicated exercise (moderate-vigorous physical activity) was the most efficient at improving fitness. Specifically, exercise was three times more efficient than walking alone and more than 14 times more efficient than reducing the time spent sedentary. Additionally, they found that the greater time spent exercising and higher steps/day could partially offset the negative effects of being sedentary in terms of physical fitness.

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In the largest study performed to date to understand the relationship between habitual physical activity and physical fitness, researchers from Boston University School of Medicine (BUSM) have found that higher amount of time spent performing exercise (moderate-vigorous physical activity) and low-moderate level activity (steps) and less time spent sedentary, translated to greater physical fitness.

“By establishing the relationship between different forms of habitual physical activity and detailed fitness measures, we hope that our study will provide important information that can ultimately be used to improve physical fitness and overall health across the life course,” explained corresponding author Matthew Nayor, MD, MPH, assistant professor of medicine at BUSM.

He and his team studied approximately 2,000 participants from the community-based Framingham Heart Study who underwent comprehensive cardiopulmonary exercise tests (CPET) for the “gold standard” measurement of physical fitness. Physical fitness measurements were associated with physical activity data obtained through accelerometers (device that measures frequency and intensity of human movement) that were worn for one week around the time of CPET and approximately eight years earlier.

They found dedicated exercise (moderate-vigorous physical activity) was the most efficient at improving fitness. Specifically, exercise was three times more efficient than walking alone and more than 14 times more efficient than reducing the time spent sedentary. Additionally, they found that the greater time spent exercising and higher steps/day could partially offset the negative effects of being sedentary in terms of physical fitness.

According to the researchers, while the study was focused on the relationship of physical activity and fitness specifically (rather than any health-related outcomes), fitness has a powerful influence on health and is associated with lower risk of cardiovascular disease, diabetes, cancer and premature death. “Therefore, improved understanding of methods to improve fitness would be expected to have broad implications for improved health,” said Nayor, a cardiologist at Boston Medical Center.

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Fitness

Tips to avoid common running injuries

Injuries are very common among runners. Recent research estimates that 82% of runners will become injured during their running career and up to 90% will experience injury while training for a marathon. Some of the most common include a stress fracture, plantar fasciitis, hamstring tendinitis, ankle sprain, runners’ knee, and Achilles’ tendonitis.

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Photo by Malik Skydsgaard from Unsplash.com

Whether training for a marathon or preparing for your first community race, being knocked off course with pain can be hard to handle mentally and physically.

Injuries are very common among runners. Recent research estimates that 82% of runners will become injured during their running career and up to 90% will experience injury while training for a marathon. Some of the most common include a stress fracture, plantar fasciitis, hamstring tendinitis, ankle sprain, runners’ knee, and Achilles’ tendonitis.

Injury prevention is critical. Here are some safety tips from Dr. Joshua Blomgren, a 15-time Chicago Marathon team physician and sports medicine physician, Midwest Orthopaedics at Rush:

Don’t over-train

Don’t increase weekly mileage or intensity by more than 10 percent each week. Build up slowly and let a good training schedule determine how much you run.

Invest in good shoes

Go to a specialty running shop to be properly fitted for running shoes and/or orthotics. Replace them every 350-500 miles. Incorrect shoes can affect your gait, leading to injuries in your feet, legs, knees, or hips.

Choose the best running surface

Look for running surfaces that absorb shock. Opt for asphalt over concrete. Find grass or dirt trails, especially for higher mileage. Avoid uneven surfaces and seek paths with slow curves.

Stretch!

Training causes tight muscles, leading to strain and changes in your gait. Commit to a stretching program. Just 5 -10 minutes after each workout can make a big difference.

Strengthen muscles

Runners have tight hip flexors because their quads are overtrained. Strengthen your hamstrings and glutes to reduce chance of injury and abductors, adductors, and core to create stability.

Watch out for heel striking

Heel striking occurs when your feet land in front of you and your heel hits the ground first. This is common among new runners but can lead to injuries such as shin splints, stress fractures, and joint pain. Land mid-sole with your foot directly underneath your body.

Prioritize posture

Good form means staying upright and keeping your shoulders back and relaxed. Work core exercises into your training and do posture checks every so often. Hold your head right above your shoulders and hips.

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Fitness

Postmenopausal women can dance their way to better health

After menopause, women are more likely to experience weight gain, overall/central body adiposity increases, and metabolic disturbances, such as increases in triglycerides and bad cholesterol. Together, these changes ultimately increase cardiovascular risk. Around this same time, women often are less physically active, which translates into reductions in lean mass and an increased risk of falls and fractures.

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Photo by Olivia Bauso from Unsplash.com

Women often struggle with managing their weight and other health risk factors, such as high cholesterol, once they transition through menopause. A new study suggests that dancing may effectively lower cholesterol levels, improve fitness and body composition and in the process, improve self-esteem. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

After menopause, women are more likely to experience weight gain, overall/central body adiposity increases, and metabolic disturbances, such as increases in triglycerides and bad cholesterol. Together, these changes ultimately increase cardiovascular risk. Around this same time, women often are less physically active, which translates into reductions in lean mass and an increased risk of falls and fractures. As a result of all these changes, postmenopausal women often suffer from decreased self-image and self-esteem, which are directly related to overall mental health.

Physical activity has been shown to minimize some of the many health problems associated with menopause. The effect of dancing, specifically, has already been investigated with regard to how it improves body composition and functional fitness. Few studies, however, have investigated the effects of dance on body image, self-esteem, and physical fitness together in postmenopausal women.

This new study was designed to analyze the effects of dance practice on body composition, metabolic profile, functional fitness, and self-image/self-esteem in postmenopausal women. Although the sample size was small, the study suggested some credible benefits of a three-times-weekly dance regimen in improving not only the lipid profile and functional fitness of postmenopausal women but also self-image and self-esteem.

Dance therapy is seen as an attractive option because it is a pleasant activity with low associated costs and low risk of injury for its practitioners. Additional confirmed benefits of regular dancing include improvement in balance, postural control, gait, strength, and overall physical performance. All of these benefits may contribute to a woman’s ability to maintain an independent, high-quality lifestyle throughout her lifespan.

Study results are published in the article “Dance practice modifies functional fitness, lipid profile, and self-image in postmenopausal women.”

“This study highlights the feasibility of a simple intervention, such as a dance class three times weekly, for improving not only fitness and metabolic profile but also self-image and self-esteem in postmenopausal women. In addition to these benefits, women also probably enjoyed a sense of camaraderie from the shared experience of learning something new,” says Dr. Stephanie Faubion, NAMS medical director.

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