Statins do not increase muscle injury after prolonged walking, important for heart health in statin users.

Statin therapy does not exacerbate muscle injury, pain or fatigue in people engaging in moderate-intensity exercises, such as walking, according to a study published today in the Journal of the American College of Cardiology. The findings reassure people who experience muscle pain or fatigue from statins but need physical activity to keep their cholesterol levels low and their hearts healthy.

Statins have long been the gold standard for lowering LDL or “bad” cholesterol and preventing cardiovascular disease (CVD) events. Still, while generally well-tolerated, they can cause muscle pain and weakness in some. Physical activity is also a cornerstone of CVD prevention, especially when combined with statins; however, studies have shown vigorous exercise can increase muscle damage in some statin users, leading to decreased physical activity or causing people to stop taking their medication. Less is known about the impact of moderate exercise.

Researchers sought to compare the impact of moderate-intensity exercise on muscle injury in symptomatic and asymptomatic statin users, plus nonstatin using controls. Symptomatic vs. asymptomatic was determined by the presence, localization and onset of muscle cramps, pain and/or weakness using the statin myalgia clinical index score. Researchers also examined the association between leukocyte CoQ10 levels on muscle injury and muscle complaints, since statins may lower CoQ10 levels and reduced levels can predispose people to muscle injury.

All study participants walked 30, 40 or 50 km (18.6, 24.8 or 31 miles, respectively) per day at a self-selected pace for four consecutive days. Statin users had all been on the medication for at least three months. The researchers excluded those with diabetes, hypo- or hyperthyroidism, known hereditary skeletal muscle defects, other diseases known to cause muscle symptoms or those using CoQ10 supplementation. There were no differences in body mass index, waist circumference, physical activity levels or vitamin D3 levels (low vitamin D3 levels have been associated with statin-induced myopathy and therefore may be a risk-factor for statin-associated muscle symptoms) among the three groups at baseline.

Researchers found that statins did not exacerbate muscle injury or muscle symptoms after moderate-intensity exercise.

“Even though muscle pain and fatigue scores were higher in symptomatic statin users at baseline, the increase in muscle symptoms after exercise was similar among the groups,” said Neeltje Allard, MD, first author of the study and researcher at the Department of integrative physiology, Radboud University Medical Center in Nijmegen, Netherlands. “These results demonstrate that prolonged moderate-intensity exercise is safe for statin users and can be performed by statin users to maintain a physically active lifestyle and to derive its cardiovascular health benefits.”

Researchers did not find a correlation between leukocyte CoQ10 levels and muscle injury markers at baseline or after exercise nor was there a correlation between CoQ10 levels and muscle fatigue resistance or muscle pain scores.

In an accompanying editorial comment, Robert Rosenson, MD, Director of Metabolism and Lipids for the Mount Sinai Health System in New York, said patients experiencing statin associated muscle symptoms will often avoid exercise because of muscle pain and weakness and concerns of making the pain worse; however, exercise is essential for restoring and maintaining fitness in people at increased risk for cardiovascular disease or who have had a cardiovascular event.

“[Based on the study], many patients who develop statin associated muscle symptoms may engage in a moderately intensive walking program without concern for worsened muscle biomarkers or performance,” he said.

Cold temperatures activate a cellular cleansing mechanism that breaks down defective protein aggregations: Expression of PSME3 in the germline, neurons and nematode gut. CREDIT David Vilchez and Hyun Ju Lee

Cold activates a cellular cleansing mechanism that breaks down harmful protein aggregations responsible for various diseases associated with aging. In recent years, studies on different model organisms have already shown that life expectancy increases significantly when body temperature is lowered. However, precisely how this works has still been unclear in many areas. A research team at the University of Cologne’s CECAD Cluster of Excellence in Aging Research has now unlocked one responsible mechanism. The study ‘Cold temperature extends longevity and prevents disease-related protein aggregation through PA28γ-induced proteasomes’ has appeared in Nature Aging.

Professor Dr David Vilchez and his working group used a non-vertebrate model organism, the nematode Caenorhabditis elegans, and cultivated human cells. Both carried the genes for two neurodegenerative diseases which typically occur in old age: amyotrophic lateral sclerosis (ALS) and Huntington’s disease. Both diseases are characterized by accumulations of harmful and damaging protein deposits – so-called pathological protein aggregations. In both model organisms, cold actively removed the protein clumps, thus preventing the pathological protein aggregation in both ALS and Huntington’s disease.

More precisely, the scientists explored the impact of cold on the activity of proteasomes, a cellular mechanism that removes damaged proteins from cells. The research revealed that the proteasome activator PA28γ/PSME3 mitigated the deficits caused by aging in both the nematode and in the human cells. In both cases, it was possible to activate proteasome activity through a moderate decrease in temperature. “Taken together, these results show how over the course of evolution, cold has preserved its influence on proteasome regulation – with therapeutic implications for aging and aging-associated diseases,” said Professor Vilchez. 
Aging is a major risk factor for several neurodegenerative diseases associated with protein aggregation, including Alzheimer’s, Parkinson’s, Huntington’s and ALS. Vilchez added: “We believe that these results may be applied to other age-related neurodegenerative diseases as well as to other animal species.” A key finding was that the proteasome activity can also be increased by genetic overexpression of the activator. That way, disease-causing proteins can be eliminated even at the normal body temperature of 37 degrees Celsius. These results may provide therapeutic targets for aging and aging-associated diseases.
It has long been known that while extremely low temperatures can be harmful to organisms, a moderate reduction in body temperature can have very positive effects. For example, a lower body temperature prolongs the longevity of cold-blooded animals like worms, flies or fish, whose body temperature fluctuates with the temperature of the environment. However, the same phenomenon also applies to mammals, who maintain their body temperature within a narrow range no matter how cold or warm their environment is. For example, the nematode lives much longer if it is moved from the standard temperature of 20 degrees Celsius to a colder temperature of 15 degrees Celsius. And in mice, a slight decrease in body temperature of just 0.5 degrees significantly extends their lifespan. This supports the assumption that temperature reduction plays a central role in longevity in the animal kingdom and is a well-conserved evolutionary mechanism. 
Even in humans, a correlation between body temperature and lifespan has been reported. Normal human body temperature is between 36.5 and 37 degrees Celsius. While an acute drop in body temperature below 35 degrees leads to hypothermia, human body temperature fluctuates slightly during the day and even reaches a cool 36 degrees during sleep. Interestingly, a previous study reported that human body temperature has steadily declined by 0.03 degrees Celsius per decade since the Industrial Revolution, suggesting a possible link to the progressive increase in human life expectancy over the last 160 years.

Ageing, or senescent cells, which stop dividing but don’t die, can accumulate in the body over the years and fuel chronic inflammation that contributes to conditions such as cancer and degenerative disorders.

In mice, eliminating senescent cells from aging tissues can restore tissue balance and increase healthy lifespan. Now a team led by investigators at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), has found that the immune response to a virus that is ubiquitously present in human tissues can detect and eliminate senescent cells in the skin.

For the study, which is published in Cell, the scientists analyzed young and old human skin samples to learn more about the clearance of senescent cells in human tissue.

The researchers found more senescent cells in the old skin compared with young skin samples. However, in the samples from old individuals, the number of senescent cells did not increase as individuals got progressively older, suggesting that some type of mechanism kicks in to keep them in check.

Experiments suggested that once a person becomes elderly, certain immune cells called killer CD4+ T cells are responsible for keeping senescent cells from increasing. Indeed, higher numbers of killer CD4+ T cells in tissue samples were associated with reduced numbers of senescent cells in old skin.

When they assessed how killer CD4+ T cells keep senescent cells in check, the researchers found that aging skin cells express a protein, or antigen, produced by human cytomegalovirus, a pervasive herpesvirus that establishes lifelong latent infection in most humans without any symptoms. By expressing this protein, senescent cells become targets for attack by killer CD4+ T cells.

“Our study has revealed that immune responses to human cytomegalovirus contribute to maintaining the balance of aging organs,” says senior author Shawn Demehri, MD, PhD, director of the High Risk Skin Cancer Clinic at MGH and an associate professor of Dermatology at Harvard Medical School. “Most of us are infected with human cytomegalovirus, and our immune system has evolved to eliminate cells, including senescent cells, that upregulate the expression of cytomegalovirus antigens.”

These findings, which highlight a beneficial function of viruses living in our body, could have a variety of clinical applications. “Our research enables a new therapeutic approach to eliminate aging cells by boosting the anti-viral immune response,” says Demehri. “We are interested in utilizing the immune response to cytomegalovirus as a therapy to eliminate senescent cells in diseases like cancer, fibrosis and degenerative diseases.”

Demehri notes that the work may also lead to advances in cosmetic dermatology, for example in the development of new treatments to make skin look younger.

A new study from researchers at Uppsala University and Karolinska Institutet shows that children who go on to develop symptoms of autism have different activity in their brain’s visual cortex from as early as five months when looking at certain types of movement. This finding may indicate that autistic people perceive their surroundings differently, even from a very young age, which could affect their development and learning.

Autism is defined by challenges with social communication and restricted and repetitive features in behaviour and interests. However, research shows that autistic people also have different perceptions of and reactions to various stimuli. In particular, many studies have shown a connection between autism and difficulties in perceiving whole units in visual movement patterns – such as when a flock of birds forms a common movement in the sky. Integrating movement signals into an overall figure is important in correctly perceiving how objects and surfaces move in relation to the viewer.

The new study examined activity in the brains of five-month-old infants sitting on their parent’s laps while viewing different types of visual information. The researchers measured how the brain reacted to simple visual changes in light (such as a line changing direction) and more complex patterns where the ability to see whole units were tested. The assessment used EEG technology, which records weak electrical signals created naturally in the brain’s cerebral cortex when processing information. The signals were measured using electrodes placed around the head on a specially adapted cap.

The infants who later on – at age three – exhibited many of the classic symptoms of autism had different brain activity when complex movement patterns were shown on the screen. This suggests that the brains of autistic people process visual motion differently from early infancy. On the other hand, simpler visual changes produced a clear and similar response in all of the children’s brains.

“Seeing this difference several years before the symptoms of autism develop is something completely new and contributes to our understanding of what early development looks like in autism. Autism has a strong hereditary component, and the differences we see in visual perception in infancy are likely connected to genetic differences,” explains Terje Falck-Ytter, Professor at the Department of Psychology at Uppsala University and principal of the study.

“We can only guess at the infant’s subjective experience of visual motion. However, given the results and previous studies of the relationship between brain activity and experience in adults with the diagnosis, it is plausible to believe that they experience it differently. It is also possible that this finding relates to the perception of complex social movements, such as the interpretation of facial expressions. This is something we want to investigate in future studies.”

The study is part of the larger research project EASE (Early Autism Sweden), a collaboration between Uppsala University and the Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND). When the children were three years old, a standardised play observation was carried out with a psychologist based on this. Each child received a score corresponding to symptoms of autism. The study also included a control group of over 400 infants, meaning the researchers had good knowledge of how children’s brains usually react to these stimuli.

“Autism cannot currently be diagnosed with good accuracy until around 2–3 years of age, but we hope that more knowledge about early development will enable us to make these assessments earlier. This would make it easier for families to get support and hopefully individualised training sooner. It could also stimulate completely new research into early interventions. The results of this study showed statistically significant differences between groups. Still, it is important to emphasise that the EEG measurement’s accuracy was too low to predict the development of individual children. It is, therefore, too early to tell whether this method will have clinical value for early detection, for example,” concludes Falck-Ytter.