Archive for the ‘aging’ Category

“No pain, no gain.” So say those working out to build up their muscles, and on a cellular level it is a pretty accurate description of how muscle mass increases. Exercise causes tears in muscle membrane and the healing process produces an increased amount of healthy muscle. Implicit in this scenario is the notion that muscle repair is an efficient and ongoing process in healthy individuals. However, the repair process is not well understood. New University of Iowa research into two types of muscular dystrophy now has opened the door on a muscle repair process and identified a protein that plays a critical role.

The protein, called dysferlin, is mutated in two distinct muscular dystrophies known as Miyoshi Myopathy and limb-girdle muscular dystrophy type 2b. The UI study suggests that in these diseases, the characteristic, progressive muscle degeneration is due to a faulty muscle-repair mechanism rather than an inherent weakness in the muscle’s structural integrity. The research findings reveal a totally new cellular cause of muscular dystrophy and may lead to many discoveries about normal muscle function and to therapies for muscle disorders.

The research team led by Kevin Campbell, Ph.D., the Roy J. Carver Chair of Physiology and Biophysics and interim head of the department, UI professor of neurology, and a Howard Hughes Medical Institute (HHMI) Investigator, studied the molecular consequences of losing dysferlin and discovered that without dysferlin muscles were unable to heal themselves.

The UI team genetically engineered mice to lack the dysferlin gene. Just like humans with Miyoshi Myopathy and limb-girdle muscular dystrophy type 2b, the mice developed a muscular dystrophy, which gets progressively worse with age. However, treadmill tests revealed that the muscles of mice that lack dysferlin were not much more susceptible to damage than the muscles of normal mice. This contrasts with most muscular dystrophies of known cause where genetic mutations weaken muscle membranes and make muscles more prone to damage.

“This told us that the dystrophies caused by dysferlin loss were very different in terms of how the disease process works compared to other dystrophies we have studied,” Campbell said. “We were gradually picking up clues that showed we had a different type of muscular dystrophy here.”

Most muscular dystrophy causing genetic mutations have been linked to disruption of a large protein complex that controls the structural integrity of muscle cells. The researchers found that dysferlin was not associated with this large protein complex. Rather, dysferlin is normally found throughout muscle plasma membrane and also in vesicles, which are small membrane bubbles that encapsulate important cellular substances and ferry them around cells. Vesicles also are important for moving membrane around in cells.

Previous studies have shown that resealing cell membranes requires the accumulation and fusing of vesicles to repair the damaged site.

Using an electron microscope to examine muscles lacking dysferlin, the UI team found that although vesicles gathered at damaged membrane sites, the membrane was not resealed. In contrast, the team discovered that when normal muscle is injured, visible “patches” form at the damaged sites, which seal the holes in the membrane. Chemicals that tag dysferlin proved that these “patches” were enriched with dysferlin and the patches appeared to be formed by the fusion of dysferlin-containing vesicles that traveled though the cell to the site of membrane damage.

The researchers then used a high-powered laser and a special dye to visualize the repair process in real time.

Under normal conditions, the dye is unable to penetrate muscle membrane. However, if the membrane is broken the dye can enter the muscle fiber where it fluoresces. Using the laser to damage a specific area of muscle membrane, the researchers could watch the fluorescence increase as the dye flowed into the muscle fiber.

“The more dye that entered, the more fluorescence we saw,” Campbell explained. “However, once the membrane was repaired, no more dye could enter and the level of fluorescence remained steady. Measuring the increase in fluorescence let us measure the amount of time that the membrane stayed open before repair sealed the membrane and prevented any more dye from entering.”

In the presence of calcium, normal membrane repaired itself in about a minute. In the absence of calcium, vesicles gathered at the damaged muscle membrane, but they did not fuse with each other or with the membrane and the membrane was not repaired. In muscle that lacked dysferlin, even in the presence of calcium, the damaged site was not repaired.

Campbell speculated that dysferlin, which contains calcium-binding regions, may be acting as a calcium sensor and that the repair system needs to sense the calcium in order to initiate the fusion and patching of the hole. Campbell added that purifying the protein and testing its properties should help pin down its role in the repair process.

The discovery of a muscle repair process and of dysferlin’s role raises many new questions. In particular, Campbell wonders what other proteins might be involved and whether defects in those components could be the cause of other muscular dystrophies.

“This work has described a new physiological mechanism in muscle and identified a component of this repair process,” Campbell said. “What is really exciting for me is the feeling that this is just a little hint of a much bigger picture.”

In addition to Campbell, the UI researchers included Dimple Bansal, a graduate student in Campbell’s laboratory and the lead author of the paper, Severine Groh, Ph.D., and Chien-Chang Chen, Ph.D., both UI post-doctoral researchers in physiology and biophysics and neurology, and Roger Williamson, M.D., UI professor of obstetrics and gynecology. Also part of the research team were Katsuya Miyake, Ph.D., a postdoctoral researcher, and Paul McNeil, Ph.D., a professor of cellular biology and anatomy at the Medical College of Georgia in Augusta, Ga., and Steven Vogel, Ph.D., at the Laboratory of Molecular Physiology at the National Institute of Alcohol Abuse and Alcoholism, Rockville, Md.

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Article adapted by MD Sports from original press release.
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Contact: Jennifer Brown
University of Iowa 

The study was funded by a grant from the Muscular Dystrophy Association.

University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide.

Scientists have discovered that a group of chemicals known as Histone Deacetylase (HDAC) inhibitors stimulate growth and regeneration of adult skeletal muscle cells by increasing expression of the protein follistatin. The research, published in the May issue of Developmental Cell, may provide new avenues for developing effective means to promote regeneration in muscular dystrophies.

Dr. Vittorio Sartorelli from the Muscle Gene Expression Group in the Laboratory of Muscle Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, in Bethesda, Maryland, and colleagues at the Salk Institute and the Dulbecco Telethon Institute in Rome report that HDAC inhibitors, which stimulate the formation of mature muscle cells from immature precursor cells, also cause a significant elevation of follistatin levels. When follistatin levels are reduced, then HDAC inhibitors no longer stimulate adult muscle growth. The regeneration activities of the HDAC inhibitors appear to function only in skeletal muscle, since follistatin is not stimulated in other cell types tested. In animal studies, administration of an HDAC inhibitor produced clear signs of muscle regeneration in regions of injured skeletal muscle tissues.

“Our findings establish for the first time that follistatin promotes the recruitment and fusion of immature muscle cells to pre-existing adult muscle fibers. These results suggest that follistatin is a promising target for future drug development of muscle regeneration. HDAC inhibitors, by stimulating follistatin, could well be pharmacologically useful as stimulants of muscle regeneration. We are investigating whether these inhibitors are a viable treatment to regenerate healthy new muscle tissues in animal models of muscular dystrophies,” explains Dr. Sartorelli. The functional link between HDAC inhibitors, follistatin, and adult muscle regeneration is especially provocative as an HDAC inhibitor is already being used clinically in humans as an anti-cancer therapeutic.

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Article adapted by MD Sports from original press release.
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Contact: Heidi Hardman
Cell Press 

Simona Iezzi, Monica Di Padova, Carlo Serra, Giuseppina Caretti, Cristiano Simone, Eric Maklan, Giulia Minetti, Po Zhao, Eric P. Hoffman, Pier Lorenzo Puri, and Vittorio Sartorelli: “Deacetylase Inhibitors Increase Muscle Cell Size by Promoting Myoblast Recruitment and Fusion through Induction of Follistatin”

 

ATHENS, Ohio – Men over 60 may be able to increase their strength by as much as 80 percent by performing intense weight training exercises, according to physiologists involved in studies of the health benefits of weight lifting. The researchers also have found that older men gain strength at the same rate as men in their 20s.

In a study of 18 men ages 60 to 75, Ohio University physiologists found that subjects who participated in a 16-week, high-intensity resistence training program on average were 50 percent to 80 percent stronger by the end of the study. None of the participants had engaged in weight lifting prior to the study. Researchers also observed improvements in the seniors’ muscle tone, aerobic capacity and cholesterol profile.

These are some of the latest findings from a decades-long examination of the impact of exercise on the health of men and women of all ages. When researchers compared the strength gains of the elderly participants in this study to findings from other studies they’ve done of college-age men, they found that changes in strength and muscle size were similar in both age groups. The findings were published in a recent issue of the Journal of Gerontology.

“There have been a number of research projects that have come out over the years that suggest there is no age limitation to getting stronger from resistance training,” said Robert Staron, co-author of this study and an associate professor of anatomy in the university’s College of Osteopathic Medicine. “It’s become obvious that it’s important to maintain a certain amount of muscle mass as we age.”

This new study also suggests that elderly men can handle heavy workloads over a long period of time. Participants – who all were in good health and closely monitored during testing and training – performed leg presses, half squats and leg extensions twice a week to exercise the lower body. When the men began the study, they were able to leg press about 375 pounds on average. After the 16-week period, they could take on about 600 pounds. Studies elsewhere have involved low-intensity exercises over a shorter term.

In addition to the increase in strength, researchers found that weight lifting had a beneficial impact on the participants’ cardiovascular system. Tests on an exercise treadmill showed that their bodies used oxygen more efficiently after weight training.

“The individuals run until they are completely exhausted, and it took longer for them to reach that point after resistance training,” Staron said.

Blood samples taken before and after weight training also showed favorable changes in participants’ overall cholesterol profiles, he said, including increases in HDL cholesterol levels and decreases in LDL cholesterol levels.

Losing muscle tone and strength is not uncommon for many senior citizens, Staron said, but this research suggests that a lack of physical exercise can contribute to the problem.

“Certainly, inactivity does play a role in contributing to the decrease in muscle mass,” Staron said. “If we can maintain a certain level of strength through exercise, our quality of life should be better as we age.”

Before beginning a weight lifting regimen, it’s a good idea to consult a physician, Staron advised, adding that it’s also important to learn proper weight lifting techniques. Staron and his colleagues now have turned their attention to how certain weight training routines impact young people.

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Article adapted by MD Sports from original press release.
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Contact: Andrea Gibson
Ohio University

Collaborators on this project are Fredrick Hagerman, Robert Hikida and Thomas Murray of the College of Osteopathic Medicine, former graduate student Seamus Walsh, Roger Gilders of the College of Health and Human Services, Kumika Toma of the College of Arts and Sciences and Kerry Ragg of the Student Health Service.

The University of Manchester is investigating whether increasing the testosterone levels of frail elderly men could improve their strength, energy and mobility.

This is the first study in the world to examine how testosterone treatment may impact this age-group, led by Professor Fred Wu of the Department of Endocrinology at Manchester Royal Infirmary.

Professor Wu said: “Levels of the male hormone testosterone fall by about 1% a year in men over 40, leading to decreases in muscle size and strength, increased body fat and thinner bones. The changes are also associated with decreased sexual interest, fatigue, mobility problems, depression, increased risk of falling and a general sense of weakness.

“Tests on younger and healthy older men suggest that testosterone replacement could help reverse these symptoms in the frail and elderly.”

Professor Wu’s team is expecting to publish the results in two years’ time, and hopes that if the treatment is proven to be effective it may be adopted as standard practice by the NHS.

As well as increasing strength, mobility and quality of life for elderly men, the move could significantly reduce the accident-rate and care requirements of this group and ultimately reduce demands on the NHS and social services.

Men aged 65+ who have lost weight, are easily tired, slow in walking and feel generally weak for no specific reason are being recruited for the study. Only those volunteers found to have low testosterone levels can be included in the trial.

The protocol for participants requires five visits to the Wellcome Trust Clinical Research Facility on Grafton Street at Manchester Royal Infirmary over the 12 month period. They will receive either testosterone or a dummy placebo in the form of a gel self-applied daily to the skin, for the first six months of the trial. Their muscle strength, mobility, bone-strength, muscle and fat content and general quality of life will then be assessed by the research team after both six and 12 months.

The research is being undertaken in partnership with Central Manchester and Manchester Children’s University Hospitals NHS Trust. Participants are free to withdraw from the study at any time, and all information will be collected in the strictest confidence.

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Article adapted by MD Sports from original press release.
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Contact: Jo Nightingale or Rachael McGraw
University of Manchester

NOTES FOR EDITORS

The University of Manchester (www.manchester.ac.uk) was formed by the merger of The Victoria University of Manchester and UMIST in October 2004, and with 36,000 students is the largest higher education institution in the country. Its Faculty of Medical & Human Sciences (www.mhs.manchester.ac.uk) is one of the largest faculties of clinical and health sciences in Europe, with a research income of over £37 million.

The School of Medicine (www.medicine.manchester.ac.uk) is the largest of the Faculty’s five Schools, with 1300 staff, almost 2000 undergraduates and a £32M research income. The School encompasses five teaching hospitals, and is closely linked to a range of general hospitals and community practices across the North West of England.

University Park, Pa. – Female athletes often lose their menstrual cycle when training strenuously, but researchers have long speculated on whether this infertility was due to low body fat, low weight or exercise itself. Now, researchers have shown that the cause of athletic amenorrhea is more likely a negative energy balance caused by increasing exercise without increasing food intake.

“A growing proportion of women are susceptible to losing their menstrual cycle when exercising strenuously,” says Dr. Nancy I. Williams, assistant professor of kineseology and physiology at Penn State. “If women go six to 12 months without having a menstrual cycle, they could show bone loss. Bone densities in some long distance runners who have gone for a prolonged time period without having normal menstrual cycles can be very low.”

In studies done with monkeys, which show menstrual cyclicity much like women, researchers showed that low energy availability associated with strenuous exercise training plays an important role in causing exercise-induced amenorrhea. These researchers, working at the University of Pittsburgh, published findings in the Journal of Clinical Endocrinology and Metabolism showing that exercise-induced amenorrhea was reversible in the monkeys by increasing food intake while the monkeys still exercised.

Williams worked with Judy L. Cameron, associate professor of psychiatry and cell biology and physiology at the University of Pittsburgh. Dana L. Helmreich and David B. Parfitt, then graduate students, and Anne Caston-Balderrama, at that time a post-doctoral fellow at the University of Pittsburgh, were also part of the research team. The researchers decided to look at an animal model to understand the causes of exercise-induced amenorrhea because it is difficult to closely control factors, such as eating habits and exercise, when studying humans. They chose cynomolgus monkeys because, like humans, they have a menstrual cycle of 28 days, ovulate in mid-cycle and show monthly periods of menses.

“It is difficult to obtain rigorous control in human studies, short of locking people up,” says Williams.

Previous cross-sectional studies and short-term studies in humans had shown a correlation between changes in energy availability and changes in the menstrual cycle, but those studies were not definitive.

There was also some indication that metabolic states experienced by strenuously exercising women were similar to those in chronically calorie restricted people. However, whether the increased energy utilization which occurs with exercise or some other effect of exercise caused exercise-induced reproductive dysfunction was unknown.

“The idea that exercise or something about exercise is harmful to females was not definitively ruled out,” says Williams. “That exercise itself is harmful would be a dangerous message to put out there. We needed to look at what it was about exercise that caused amenorrhea, what it was that suppresses ovulation. To do that, we needed a carefully controlled study.”

After the researchers monitored normal menstrual cycles in eight monkeys for a few months, they trained the monkeys to run on treadmills, slowly increasing their daily training schedule to about six miles per day. Throughout the training period the amount of food provided remained the standard amount for a normal 4.5 to 7.5 pound monkey, although the researchers note that some monkeys did not finish all of their food all of the time.

The researchers found that during the study “there were no significant changes in body weight or caloric intake over the course of training and the development of amenorrhea.” While body weight did not change, there were indications of an adaptation in energy expenditure. That is, the monkeys’ metabolic hormones also changed, with a 20 percent drop in circulating thyroid hormone, suggesting that the suppression of ovulation is more closely related to negative energy balance than to a decrease in body weight.

To seal the conclusion that a negative energy balance was the key to exercise-induced amenorrhea, the researchers took four of the previous eight monkeys and, while keeping them on the same exercise program, provided them with more food than they were used to. All the monkeys eventually resumed normal menstrual cycles. However, those monkeys who increased their food consumption most rapidly and consumed the most additional food, resumed ovulation within as little as 12 to 16 days while those who increased their caloric intake more slowly, took almost two months to resume ovulation.

Williams is now conducting studies on women who agree to exercise and eat according to a prescribed regimen for four to six months. She is concerned because recreational exercisers have the first signs of ovulatory suppression and may easily be thrust into amenorrhea if energy availability declines. Many women that exercise also restrict their calories, consciously or unconsciously.

“Our goal is to test whether practical guidelines can be developed regarding the optimal balance between calories of food taken in and calories expended through exercise in order to maintain ovulation and regular menstrual cycles,” says Williams. “This would then ensure that estrogen levels were also maintained at healthy levels. This is important because estrogen is a key hormone in the body for many physiological systems, influencing bone strength and cardiovascular health, not just reproduction.”

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Article adapted by MD Sports from original press release.
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Contact: A’ndrea Elyse Messer
Penn State

New study dispels belief that increasing the hormone level improves the sexual function

Bethesda, Md.— The American Journal of Physiology: Endocrinology and Metabolism, one of the 14 peer-reviewed journals published by the American Physiological Society (APS), spotlights recent research findings designed to improve and understand human well-being and health. A study in the December edition examines how different doses of testosterone affect body composition, muscle size, strength, and sexual functions.

Background

Testosterone regulates many physiological processes, including muscle protein metabolism, some aspects of sexual and cognitive functions, secondary sex characteristics, erythropoiesis, plasma lipids, and bone metabolism. However, testosterone dose dependency of various hormonal dependent functions has not been well understood in the scientific community. Previous studies reveal that administration of replacement doses of testosterone to hypogonadal men and of supraphysiological doses to eugonadal men increases fat-free mass, muscle size, and strength. Conversely, suppression of endogenous testosterone concentrations is associated with loss of fat-free mass and a decrease in fractional muscle protein synthesis.

What is not known is whether testosterone effects on the muscle are dose dependent, or the nature of the testosterone dose-response relationships. Animal studies suggest that different androgen-dependent processes have different androgen dose-response relationships. Sexual function in male mammals is maintained at serum testosterone concentrations that are at the lower end of the male range. However, it is not known whether the low normal testosterone levels that normalize sexual function are sufficient to maintain muscle mass and strength, or whether the higher testosterone concentrations required to maintain muscle mass and strength might adversely affect plasma lipids, hemoglobin levels, and the prostate.

The Study

The primary objective of this study was to determine the dose dependency of testosterone’s effects on fat-free mass and muscle performance. The authors hypothesized that changes in circulating testosterone concentrations would be associated with dose-dependent changes in fat-free mass, muscle strength, and power in conformity with a single linear dose-response relationship, and that the dose requirements for maintaining other androgen-dependent processes would be different.

Young men were treated with a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion, and concomitantly also with one of five testosterone-dose regimens to create different levels of serum testosterone concentrations extending from subphysiological to the supraphysiological range. The lowest testosterone dose, 25 mg weekly, was selected because this dose had been shown to maintain sexual function in GnRH antagonist-treated men. The selection of the 600-mg weekly dose was based on the consideration that this was the highest dose that had been safely administered to men in controlled studies.

The authors of the study, “Testosterone Dose-Response Relationships in Healthy Young Men” are Shalender Bhasin, Linda Woodhouse, Connie Dzekov, Jeanne Dzekov, Indrani Sinha-Hikim, Ruoquing Shen, and Atam B. Singh, all from the Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA; Richard Casaburi, Dimple Bhasin, Nancy Berman, Rachelle Bross and Jeffrey Phillips, from the Harbor-University of California Los Angeles Medical Center, Torrance, CA; Xianghong Chen and Kevin E. Yarasheski at the Biomedical Mass Spectrometric Research Resource, Department of Internal Medicine, Washington University, School of Medicine, St. Louis, Missouri, Lynne Magliano and Thomas W. Storer, from the Laboratory for Exercise Sciences, El Camino College, El Camino, CA.

Protocol

This was a double-blind, randomized study consisting of a four-week control period, a 20-week treatment period, and a 16-week recovery period. The participants were healthy men, 18-35 years of age, with prior weight-lifting experience and normal testosterone levels. These men had not used any anabolic agents and had not participated in competitive sports events in the preceding year, and they were not planning to participate in competitive events in the following year. The participants were asked not to undertake strength training or moderate-to-heavy endurance exercise during the study. These instructions were reinforced every four weeks.

Sixty-one eligible men were randomly assigned to one of five groups. All received monthly injections of a long-acting GnRH agonist to suppress endogenous testosterone production. In addition, group 1 received 25 mg of testosterone enanthate intramuscularly weekly; group 2, 50 mg testosterone enanthate; group 3, 125 mg testosterone enanthate; group 4, 300 mg testosterone enanthate; and group 5, 600 mg testosterone enanthate. Twelve men were assigned to group 1, 12 to group 2, 12 to group 3, 12 to group 4, and 13 to group 5.

Nutritional Intake

Energy and protein intakes were standardized at 36 kcal/kg. The standardized diet was initiated two weeks before treatment started; dietary instructions were reinforced every four weeks. The nutritional intake was verified by analysis of three-day food records and 24-hour food recalls every four weeks.

Outcome Measures

Body composition and muscle performance were assessed at baseline and during week 20. Fat-free mass and fat mass were measured by underwater weighing and dual-energy X-ray absorptiometry. Total thigh muscle and quadriceps muscle volumes were measured by MRI scanning.

For estimation of total body water, the men ingested 10 g of 2H2O, and plasma samples were drawn at 0, 120, 180, and 240 min. A measurement of 2H abundance in plasma was made by nuclear magnetic resonance spectroscopy, with a correction factor of 0.985 for exchangeable hydrogen. Another measure of bilateral leg press strength was taken by use of the one-repetition maximum (1-RM) method. A seated leg press exercise with pneumatic resistance was used for this purpose. Subjects performed 5-10 min of leg cycling and stretching warm-up and received instruction and practice in lifting mechanics before performing progressive warm-up lifts leading to the 1-RM. Seat position and the ensuing knee and hip angles, as well as foot placement, were measured and recorded for use in subsequent testing. To ensure reliability in this highly effort-dependent test, the 1-RM score was reassessed within seven days, but not sooner than two days, after the first evaluation. If duplicate scores were within five percent, the higher of the two values was accepted as the strength score. If the two tests differed by greater than five percent, additional studies were conducted.

Sexual function was assessed by daily logs of sexual activity and desire that were maintained for seven consecutive days at baseline and during treatment by use of a published instrument. Spatial cognition was assessed by a computerized checkerboard test and mood by Hamilton’s depression and Young’s mania scales.

Adverse experiences, blood counts and chemistries, prostate-specific antigen (PSA), plasma lipids, total and free testosterone, luteinizing hormone (LH), sex steroid-binding globulin (SHBG), and insulin-like growth factor I (IGF-I) levels were measured periodically during control and treatment periods. Serum total testosterone was measured by an immunoassay.

Results

Of 61 men enrolled, 54 completed the study: 12 in group 1, 8 in group 2, 11 in group 3, 10 in group 4, and 13 in group 5. One man discontinued treatment because of acne; other subjects were unable to meet the demands of the protocol. The five groups did not significantly differ with respect to their baseline characteristics. Key findings included:

– Compliance: All evaluable subjects received 100percent of their GnRH agonist injections, and only one man in the 125-mg group missed one testosterone injection.

– Nutritional intake: Daily energy intake and proportion of calories derived from protein, carbohydrate, and fat were not significantly different among the five groups at baseline. There was no significant change in daily caloric, protein, carbohydrate, or fat intake in any group during treatment.

– Hormone levels: Serum total and free testosterone levels, measured during week 16, one week after the previous injection, were linearly dependent on the testosterone dose (P = 0.0001). Serum total and free testosterone concentrations decreased from baseline in men receiving the 25- and 50-mg doses and increased at 300- and 600-mg doses. Serum LH levels were suppressed in all groups. Serum SHBG levels decreased dose dependently at the 300- and 600-mg doses but did not change in other groups. Serum IGF-I concentrations increased dose dependently at the 300- and 600-mg doses.

– Body composition: Fat-free mass, measured by underwater weighing, did not change significantly in men receiving the 25- or 50-mg testosterone dose, but it increased dose dependently at higher doses. The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log total testosterone concentrations during treatment (r = 0.73, P = 0.0001). Fat mass, measured by underwater weighing, increased significantly in men receiving the 25- and 50-mg doses, but did not change in men receiving the higher doses of testosterone. There was an inverse correlation between change in fat mass by underwater weighing and log testosterone concentrations.

– Muscle size: The thigh muscle volume and quadriceps muscle volume did not significantly change in men receiving the 25- or 50-mg doses but increased dose-dependently at higher doses of testosterone. The changes in thigh muscle and quadriceps muscle volumes correlated with log testosterone levels during treatment.

– Muscle performance: The leg press strength did not change significantly in the 25- and 125-mg-dose groups but increased significantly in those receiving the 50-, 300-, and 600-mg doses. Leg power did not change significantly in men receiving the 25-, 50-, and 125-mg doses of testosterone weekly, but it increased significantly in those receiving the 300- and 600-mg doses. The increase in leg power correlated with log testosterone concentrations and changes in fat-free mass and muscle strength.

– Behavioral measures: The scores for sexual activity and sexual desire measured by daily logs did not change significantly at any dose. Similarly, visual-spatial cognition and did not change significantly in any group.

– Adverse experiences and safety measures: Hemoglobin levels decreased significantly in men receiving the 50-mg dose but increased at the 600-mg dose; the changes in hemoglobin were positively correlated with testosterone concentrations. Changes in plasma HDL cholesterol, in contrast, were negatively dependent on testosterone dose and correlated with testosterone concentrations. Total cholesterol, plasma low-density lipoprotein cholesterol, and triglyceride levels did not change significantly at any dose. Serum PSA, creatinine, bilirubin, alanine aminotransferase, and alkaline phosphatase did not change significantly in any group, but aspartate aminotransferase decreased significantly in the 25-mg group. Two men in the 25-mg group, five in the 50-mg group, three in the 125-mg group, seven in the 300-mg group, and two in the 600-mg group developed acne. One man receiving the 50-mg dose reported decreased ability to achieve erections.

Discussion

The researchers found that GnRH agonist administration suppressed endogenous LH and testosterone secretion. Therefore, circulating testosterone concentrations during treatment were proportional to the administered dose of testosterone enanthate. This strategy of combined administration of GnRH agonist and graded doses of testosterone enanthate was effective in establishing different levels of serum testosterone concentrations among the five treatment groups. The different levels of circulating testosterone concentrations created by this regimen were associated with dose- and concentration-dependent changes in fat-free mass, fat mass, thigh and quadriceps muscle volume, muscle strength, leg power, hemoglobin, circulating IGF-I, and plasma HDL cholesterol.

Serum PSA levels, sexual desire and activity, and spatial cognition did not change significantly at any dose. The changes in fat-free mass, muscle volume, leg press strength and power, hemoglobin, and IGF-I were positively correlated, whereas changes in plasma HDL cholesterol and fat mass were negatively correlated with testosterone dose and total and free testosterone concentrations during treatment.

There were no significant changes in overall sexual activity or sexual desire in any group, including those receiving the 25-mg dose. Testosterone replacement of hypogonadal men improves frequency of sexual acts and fantasies, sexual desire, and response to visual erotic stimuli. The data demonstrate that serum testosterone concentrations at the lower end of male range can maintain some aspects of sexual function.

Conclusions

This study demonstrates that an increase in circulating testosterone concentrations results in dose-dependent increases in fat-free mass, muscle size, strength, and power. The relationships between circulating testosterone concentrations and changes in fat-free mass and muscle size conform to a single log-linear dose-response curve. The data do not support the notion of two separate dose-response curves reflecting two independent mechanisms of testosterone action on the muscle.

In addition, the study could not determine if responsiveness to testosterone is attenuated in older men. Testosterone dose-response relationships might be modulated by other muscle growth regulators, such as nutritional status, exercise and activity level, glucocorticoids, thyroid hormones, and endogenous growth hormone secretory status. Serum PSA levels decrease after androgen withdrawal, and testosterone replacement of hypogonadal men increases PSA levels into the normal range.

The data demonstrate that different androgen-dependent body functions respond differently to different testosterone dose-response relationships. Some aspects of sexual function and spatial cognition, and PSA levels, were maintained by relatively low doses of testosterone in GnRH agonist-treated men and did not increase further with administration of higher doses of testosterone. In contrast, graded doses of testosterone were associated with dose and testosterone concentration-dependent changes in fat-free mass, fat mass, muscle volume, leg press strength and power, hemoglobin, IGF-I, and plasma HDL cholesterol.

Testosterone doses associated with significant gains in fat-free mass, muscle size, and strength were associated with significant reductions in plasma HDL concentrations. Further studies are needed to determine whether clinically significant anabolic effects of testosterone can be achieved without adversely affecting cardiovascular risk. Selective androgen receptor modulators that preferentially augment muscle mass and strength, but only minimally affect prostate and cardiovascular risk factors, are desirable.

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Article adapted by MD Sports from original press release.
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Contact: Donna Krupa
American Physiological Society

Source: American Journal of Physiology: Endocrinology and Metabolism, December 2001

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

Experts at The University of Nottingham are to investigate the effect of nutrients on muscle maintenance in the hope of determining better ways of keeping up our strength as we get old.

The researchers, based at the School of Graduate Entry Medicine and Health in Derby, want to know what sort of exercise we can take and what food we should eat to slow down the natural loss of skeletal muscle with ageing.

The team from the Department of Clinical Physiology, which has over 20 years experience in carrying out this type of metabolic study, need to recruit 16 healthy male volunteers in two specific age groups to help in it’s research.

Skeletal muscles make up about half of our body weight and are responsible for controlling movement and maintaining posture. However, at around 50 years of age our muscles begin to waste at approximately 0.5 per cent to one per cent a year. It means that an 80 year old may only have 70 per cent of the muscle of a 50 year old.

Since the strength of skeletal muscle is proportional to muscle size, such wasting makes it harder to carry out daily activities requiring strength, such as climbing stairs and leads to a loss of independence and an increased risk of falls and fractures.

In order for skeletal muscles to maintain their size, the large reservoirs of muscle protein require constant replenishment in the way of amino acids from protein contained within the food we eat. In fact, amino acids from our food act not only as the building blocks of muscle proteins but also actually ‘tell’ our muscle cells to build proteins.

Recent research from the clinical physiology team has shown that the cause of muscle wasting with ageing appears to be an attenuation of muscle building in response to protein feeding. In other words, as we age we lose the ability to covert the protein in the food we eat in to muscle tissue. The proposed research will investigate the mechanisms responsible for this deficit.

Dr Philip Atherton, who is currently recruiting volunteers, said: “I am really excited to be involved in this project because if we can determine ways to better maintain muscle mass as we age it will greatly benefit us all.”

The researchers are looking for 16 healthy, non-smoking, male volunteers aged 18 to 25 and 65 to 75.

Initially, the volunteers will undergo a health screening and then on a different day, under the supervision of a doctor, will be infused with an amino acid mixture to simulate feeding along with a ‘tagged’ amino acid that allows them to assess muscle building. To make these measures, blood samples will be taken from the arm and muscle biopsies from the thigh muscle under local anaesthesia. Volunteers will receive an honorarium to cover their expenses.

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Article adapted by MD Sports from original press release.
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Contact: Lindsay Brooke
University of Nottingham

 

The study will take place at The University of Nottingham’s Medical School which based at the City Hospital in Derby.

USC study finds combining resistance training and androgens gives more muscular bang for the buck

PHILADELPHIA (June 19, 2003)-Men who take supplemental androgens-the male hormone testosterone or similar medications-increase their strength by adding muscle mass, but androgens alone do not pack more might into the muscles, according to studies presented today by University of Southern California researchers.

Treatment with androgens increases lean body mass-which encompasses everything in the body but bone and fat-and strength increases proportionately with the amount of muscle added, says E. Todd Schroeder, Ph.D., postdoctoral fellow in the Department of Medicine at the Keck School of Medicine of USC and adjunct assistant professor in the USC Department of Biokinesiology and Physical Therapy. Schroeder presented his findings at the Endocrine Society’s 85th Annual Meeting.

However, when men use androgen therapy combined with resistance training, such as weightlifting, their gains in strength may far outpace the amount of muscle that can be added with androgens alone. Each muscle cell packs a bigger punch, a concept known as improved muscle quality.

“The results of androgen therapy alone on muscle and strength are not necessarily bad, but they are not optimal,” Schroeder says. “The men did improve their strength, but it was proportional to the muscle mass they added.”

The findings wield health implications beyond the stereotypes of muscle-bound bodybuilders. Schroeder and his colleagues are studying the usefulness of androgens and exercise in helping maintain muscle strength, muscle power and physical function among seniors, for example. They also have studied androgen therapy’s effectiveness in battling wasting among HIV-positive patients.

In their recent study, Schroeder and USC colleagues Michael Terk, M.D., and Fred R. Sattler, M.D., looked at both young men and seniors. They followed two groups: 33 seniors ranging from their mid-60s to late 70s, and 23 HIV-positive men ranging from their early 30s to late 40s.

The younger men were randomly assigned to get 600 milligrams (mg) each week of nandrolone alone or in combination with resistance training. The older men were randomly assigned to receive 20 mg a day of oxandrolone or a placebo. These pharmacologic androgen doses were given over 12 weeks.

Researchers determined maximal strength-the most weight a participant could safely lift or push-using leg press, leg extension and leg flexion machines.

The researchers also measured the cross-sectional area of participants’ thighs and the lean body mass of their lower extremities by magnetic resonance imaging, or MRI. They then determined the strength that participants exerted for each unit of muscle (muscle quality) and how muscle quality changed over time.

Androgens alone increased lean body mass and maximum strength in both groups of men, but “gains were modest,” Schroeder says, and muscle quality did not change, since the muscle size and strength both increased proportionately. However, among those using nandrolone and undergoing resistance training, muscle quality improved significantly: Gains in strength were much greater than the gains that could occur from muscle-mass increase alone.

“It is clear from our studies and others that resistance training is critical for increasing muscle quality, but the effects can probably be augmented with androgens,” Schroeder says. “In addition, not everyone can do resistance training, and a short course of androgens can help get people stronger and more functional.”

Finally, results provide researchers insight into how to better design future studies to test strategies to best preserve and even improve muscle strength and physical function among seniors. Similar studies will be important for other types of patients who experience muscle loss and frailty, such as those with cancer, chronic lung disease, chronic renal failure and other conditions.

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Article adapted by MD Sports from original press release.
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Contact: Jon Weiner
University of Southern California

Grants by the National Institute of Diabetes & Digestive & Kidney Diseases and the National Center for Research Resources (General Clinical Research Center) supported the research. Bio Technology General Corp., which makes Oxandrin (oxandrolone), also supported part of the research.

Edward T. Schroeder, Michael Terk and Fred R. Sattler, “Pharmacological Doses of Androgen Do Not Improve Muscle Quality in Young or Older Men: Results from Two Studies,” Endocrine Society’s 85th Annual Meeting, poster P3-212, presentation 11 a.m., June 21. Findings released at news conference 1:30 p.m., June 19.

It’s an inevitable truth: as we get older, our muscles deteriorate and we become weaker. Not only can this be an immensely frustrating change, but it can also have many other, more serious implications. We become clumsier and begin to have more falls, often resulting in broken bones or even more severe injuries. There is wide interest in this phenomenon, but to date, the majority of research has focussed on therapies for older patients with advanced symptoms. Now one study, led by Dr Alexandra Sänger from the University of Salzburg, is taking a new approach: scientists are examining the effects of different exercise regimes in menopausal women, with the aim of developing new strategies for delaying and reducing the initial onset of age related muscle deterioration. Results will be presented on Monday 7th July at the Society for Experimental Biology’s Annual Meeting in Marseille [Poster Session A5].

Dr Sänger’s research group has investigated two particular methods of physical training. Hypertrophy resistance training is a traditional approach designed to induce muscle growth whereas ‘SuperSlow®’ is a more recently devised system which involves much slower movement and fewer repetitions of exercises, and was originally introduced especially for beginners and for rehabilitation. “Our results indicate that both methods increase muscle mass at the expense of connective and fatty tissue, but contrary to expectations, the SuperSlow® method appears to have the greatest effect,” reveals Dr Sänger. “These findings will be used to design specific exercise programmes for everyday use to reduce the risk of injury and thus significantly contribute to a better quality of life in old age.”

The study focussed on groups of menopausal women aged 45-55 years, the age group in which muscle deterioration first starts to become apparent. Groups undertook supervised regimes over 12 weeks, based on each of the training methods. To see what effect the exercise had, thigh muscle biopsies were taken at the beginning and end of the regimes, and microscopically analysed to look for changes in the ratio of muscle to fatty and connective tissue, the blood supply to the muscle, and particularly for differences in the muscle cells themselves. “The results of our experiments have significantly improved our understanding of how muscles respond to different forms of exercise,” asserts Dr Sänger. “We believe that the changes that this new insight can bring to current training systems will have a considerable effect on the lives of both menopausal and older

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Article adapted by MD Sports from original press release.
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Notes to editors

  • Hypertrophy resistance training is a method of strength training that is designed to induce muscle growth, also known as hypertrophy.
  • SuperSlow® resistance training was developed by Ken Hutchins and is based on the same principle as hypertrophy resistance training, but involves slower movement and fewer repetitions of exercises, which is thought to improve the quality of muscle contraction and thereby strength.

Contact: Holly Astley
Society for Experimental Biology

    Creatine, a popular nutritional supplement used by weightlifters and sprinters to improve athletic performance, could lend muscle strength to people with muscular dystrophies.

    Muscle strength increased by an average of 8.5 percent among patients taking creatine, compared to those who did not use the supplement, according to a recent review of studies. Creatine users also gained an average of 1.4 pounds more lean body mass than nonusers.

    The evidence from the studies “shows that short- and medium-term creatine treatment improves muscle strength in people with muscular dystrophies and is well-tolerated,” said lead reviewer Dr. Rudolf Kley of Ruhr University Bochum in Germany.

    The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

    Creatine is found naturally in the body, where it helps supply energy to muscle cells. Athletes looking for short bursts of intense strength have used creatine in powders or pills for decades, but the supplement became more popular after the 1992 Barcelona Olympics, when sprinters, rowers and cyclists went public with their creatine regimens.

    Although creatine has been widely studied as a performance enhancer, it’s still not clear if the supplement makes a difference, according to Roger Fielding, Ph.D., of Tufts University, who has also recently written a review of creatine treatments for neuromuscular diseases.

    People with muscular dystrophies can have lower-than-normal levels of creatine, along with increasing muscle weakness as their disease progresses. Since some studies suggest that creatine improves muscle performance in healthy people, many researchers have reasoned that it might be helpful in treating muscle disease.

    The Cochrane researchers reviewed 12 studies that included 266 people with different types of muscular dystrophy. People in the studies who took creatine supplements used them for three weeks to six months.

    In muscular dystrophies, the proteins that make up the muscles themselves are either missing or damaged. In a related group of disorders called metabolic myopathies, the chemicals that help muscles operate go awry.

    Although creatine seemed to help many patients with muscular dystrophies, those with metabolic myopathies gained no more muscle strength or lean body mass than patients who did not use the supplement.

    The reason for the contrasting results — creatine’s “fairly consistent” effects in muscular dystrophy and lack of effectiveness in metabolic diseases — is “not entirely clear,” Kley said, calling for more research on treatment for metabolic disorders.

    The review was supported by the Neuromuscular Center Ruhrgebiet/Kliniken Bergmannsheil, at Ruhr-University Bochum and the Hamilton Health Sciences Corporation, in Canada. Kley and colleagues have each participated in trials of creatine treatment for muscle disorders, although none of the studies was sponsored by a maker of creatine.

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    Article adapted by MD Sports from original press release.
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    FOR MORE INFORMATION
    Health Behavior News Service: hbns-editor@cfah.org

    Kley RA, Vorgerd M, Tarnopolsky MA. Creatine for treating muscle disorders. Cochrane Database of Systematic Reviews 2007, Issue 1.

    The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.