Tag: muscle strength

Categories : Ageing Regenerative MedicineTags :

Restoring Muscle Strength Lost to Aging or Injury

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A small molecule previously shown to enhance strength in injured or old laboratory mice does so by restoring lost connections between nerves and muscle fibres, Stanford Medicine researchers have found.

The molecule blocks the activity of an aging-associated enzyme, or gerozyme, called 15-PGDH that naturally increases in muscles as they age. The study, which was published in Science Translational Medicine, showed that levels of the gerozyme increase in muscles after nerve damage and that it is prevalent in muscle fibres of people with neuromuscular diseases.

The research is the first to show that damaged motor neurons can be induced to regenerate in response to a drug treatment and that lost strength and muscle mass can be at least partially regained. It suggests that, if similar results are seen in humans, the drug may one day be used to prevent muscle loss of muscle strength due to aging or disease or to hasten recovery from injury.

It’s estimated that sarcopenia, or debilitating muscle frailty, affects about 30% of people over 80 and costs the United States around $380 billion each year.

“There is an urgent, unmet need for drug treatments that can increase muscle strength due to aging, injury or disease,” said Helen Blau, PhD, professor of microbiology and immunology. “This is the first time a drug treatment has been shown to affect both muscle fibres and the motor neurons that stimulate them to contract in order to speed healing and restore strength and muscle mass. It’s unique.”

Blau, the Donald E. and Delia B. Baxter Foundation Professor and director of the Baxter Laboratory for Stem Cell Biology, is the senior author of the study. Postdoctoral scholar Mohsen Bakooshli, PhD, and former postdoctoral scholar Yu Xin Wang, PhD, are the lead authors of the study. Wang is now an assistant professor at the Sanford Burnham Prebys Medical Discovery Institute in San Diego.

Addressing loss of strength

The finding is the latest from the Blau laboratory focused on understanding how muscles weaken from aging or disease, and whether it’s possible to combat this decline. In 2021, the group showed that blocking the activity of 15-PGDH in 24-month-old laboratory mice significantly enhances the animals’ leg strength and endurance when running on a treadmill. (Laboratory mice typically live about 26 to 30 months.) But it wasn’t clear exactly how.

The new research shows that the effect is due to the restoration of lost connections between the nerves and the muscle. These connections, called neuromuscular junctions, are how the brain signals muscles to contract. In aging, some of these connections are lost, causing muscle contractions to become less powerful and muscles to atrophy. People typically lose muscle mass and strength, up to 10% per decade, after the age of 50.

Conditions other than aging can also destabilise these connections, including the disuse of muscles due to bedrest after illness or injury, or muscle-wasting diseases like spinal muscular atrophy or amyotrophic lateral sclerosis (also known as ALS).

Blau’s previous research showed that a molecule called PGE2 is critical to the function of stem cells in muscle fibres that repair damage – including the microtears from exercise that lead to an increase in muscle mass and strength. They subsequently showed that levels of 15-PGDH, which breaks down PGE2, increase in the muscles with age and that the loss of strength with aging could be overcome by inhibiting the activity of this PGE2-degrading enzyme.

“PGE2 is part of the body’s natural healing mechanism, and its levels increase in muscle after injury,” Blau said. “We wanted to learn how age triggers an increase in 15-PGDH, and therefore the degradation and loss of PGE2.”

A lack of nerves

The researchers knew that muscles become less innervated, or infiltrated with nerves, as people and animals age. They wondered if that loss could be what triggers the rising levels of 15-PGDH.

“We found that when you cut the nerve that innervates the leg muscles of mice, the amount of 15-PGDH in the muscle increases rapidly and dramatically,” Blau said. “This was an exciting new insight. But what surprised us most was that when these mice are treated with a drug that inhibits 15-PGDH activity, the nerve grows back and makes contact with the muscle more quickly than in control animals, and that this leads to a faster recovery of strength and function.”

Additional experiments showed that treatment with the drug restored neuromuscular junctions lost during aging and increased muscle strength and function in old laboratory mice. The researchers also identified discrete clumps of 15-PGDH in the muscle fibres of people with several types of neuromuscular disorders suggesting that the gerozyme may have a role in causing these human disorders.

Blau and her colleagues plan to investigate at a molecular level how neural growth is stimulated by blocking 15-PGDH activity. Blau has also co-founded a company, Epirium Bio, to develop similar drugs for use in humans. Although her lab is still conducting animal studies, the company hopes to launch a clinical trial within the next year or so.

“Our next steps will be to examine whether blocking 15-PGDH function in people with spinal muscular atrophy can increase lost muscle strength in combination with gene therapy or other treatments,” Blau said. “We are also looking at ALS to see if something like this might help these patients. It’s really exciting that we are able to affect both muscle function and motor neuron growth.”

Source: Stanford Medicine

Categories : Exercise Neurodegenerative DiseasesTags :

Could an Alzheimer’s Treatment be Lurking in a Bodybuilder’s Supplement?

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A safe treatment against Alzheimer’s progression may be hidden in a common bodybuilding supplement. Researchers recently discovered that a muscle-building supplement called beta-hydroxy beta-methylbutyrate (HMB), may help protect memory, reduce plaques and ultimately help prevent the progression of Alzheimer’s disease. The researchers published their results in the journal Cell Reports.

HMB is a safe over-the-counter supplement, which bodybuilders regularly use to enhance exercise-related muscle strength and growth.

“This may be one of the safest and the easiest approaches to halt disease progression and protect memory in Alzheimer’s disease patients,” said Kalipada Pahan, PhD, at RUSH Medical College.

Studies in mouse models of Alzheimer’s have shown that HMB successfully reduces plaques and increases factors for neuronal growth to protect learning and memory, according to neurological researchers at RUSH.

“Understanding how the disease works is important to developing effective drugs to protect the brain and stop the progression of Alzheimer’s disease,” Pahan said.

Previous studies indicate that a family of proteins known as neurotrophic factors are drastically decreased in the brains of people with Alzheimer’s disease and have been found to help in survival and function of neurons, which are cells that receive and send messages from the body to the brain and vice versa.

“Our study found that after oral consumption, HMB enters into the brain to increase these beneficial proteins, restore neuronal connections and improve memory and learning in mice with Alzheimer’s-like pathology, such as plaques and tangles,” Pahan said.

The study findings indicate that HMB stimulates the nuclear hormone receptor PPARα within the brain that regulates the transport of fatty acids, which is key to the success of HMB as a neuroprotective supplement.

“If mouse results with HMB are replicated in Alzheimer’s disease patients, it would open up a promising avenue of treatment of this devastating neurodegenerative disease,” Pahan said.

Source: Rush University Medical Center

Categories : ExerciseTags :

Compression Garments Offer No Exercise Recovery Benefit

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Man and woman about to sprint
Source: Andrea Piacquadio on Pexels

A meta-analysis of studies on the ability of compression garments, elastic clothing on the limbs or hips, to enhance muscle recovery after exercise found that they provide no recovery benefit. Rather, they should be used to help reduce injury, the reviewers suggest.

Use of compression garments has gained popularity over the last few decades because they are thought to enhance muscle recovery following exercise.

An international research team, led by assistant professor János Négyesi, conducted a review using a generic inverse variance model, which adjusts the weight of individual studies according to sample size, to more accurately assess the effects of compression garments than previous meta-analyses.

Contrary to results found in individual research, the meta-analytical evidence suggests that wearing a compression garment during or after training does not facilitate muscle recovery.

“Even data from our previous study supported the idea that such garments have the potential to reduce strength loss after a strenuous workout,” said Dr Négyesi. “However, when we synthesized the data of all relevant studies, we found no effect of compression garments on strength recovery – even when factoring in exercise type and when and where the compression garment is applied.”

The authors think this is a perfect example of contradictory outcomes from individual studies and meta-analytical evidence. Therefore, scientists should be careful when drawing direct conclusions from the results of their studies. Rather, meta-analyses using the most appropriate models can provide more precise and reliable results.

Overall, practitioners, athletes, coaches, and therapists should reconsider compression garments as a means of reducing the harmful effects of physical exercise on muscle strength and seek alternative methods.

The review appears in Sports Medicine.

Source: Tohoku University

Categories : AgeingTags :

Timely Interventions Could Counteract Sarcopenia

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A new study from Karolinska Institutet in Sweden suggests that the early stages of sarcopenia, where muscles weaken with age faster than expected, could be counteracted with timely interventions designed to preserve physical and cognitive function and manage chronic conditions. The study’s findings are published in the Journal of Cachexia, Sarcopenia and Muscle.

Muscle mass and function is lost with ageing. When this decline is more extensive or rapid than expected, it is categorised as sarcopenia, a common condition in the elderly that often lowers quality of life and increases fall and fracture risks.

Researchers examined how different factors such as sex, age, educational level, living arrangement, lifestyle and chronic conditions affected the development of sarcopenia in people aged 60 and above across a 12-year period.

When the study began, almost 10% of the nearly 3200 participants had sarcopenia, 27% had probable sarcopenia and just over 63% no sarcopenia. Measurements such as grip strength, walking speed, speed of rising from a chair five times and calf circumference were used to assess muscle strength and mass and physical performance.

“Perhaps the most interesting result was that after five years, a roughly equal proportion (just over 10 percent) of the individuals with probable sarcopenia had either improved or deteriorated. This suggests that sarcopenia is a dynamic condition that is modifiable especially in the initial stages, which is a hopeful message,” said corresponding author Caterina Trevisan, affiliated researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

Physical activity and higher results on cognitive tests improved odds of improvement and lowered mortality risk, while a higher number of chronic conditions, male sex and older age had the opposite correlation. For individuals initially diagnosed with severe sarcopenia, there was little chance of improvement, and many of them (almost 71%) died during the follow-up period.

“Our results support the need of early interventions to preserve physical and cognitive functions and manage chronic conditions in older individuals,” says the study’s last author Anna-Karin Welmer, senior lecturer at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “With these tools, we could probably counteract muscle deterioration and the impairment in quality of life this entails. We now need intervention studies to find ways to use these tools to counteract sarcopenia.”

Source: Karolinska Institutet

Categories : Diet and NutritionTags :

Extra Vitamin D Does not Boost Muscles

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Vitamin D supplementation does not have beneficial effects on muscle function, strength, or mass, according to a new meta-analysis, and may even have detrimental effects on muscle strength in people with normal levels of the vitamin.

Vitamin D deficiency, causes a generalised decrease in bone mineral density, resulting in osteopenia and osteoporosis. In young children who have little mineral in their skeleton, this defect results in a variety of skeletal deformities classically known as rickets. It is also believed to cause muscle weakness; affected children have difficulty in standing and walking, whereas the elderly have increasing sway and more frequent falls,thereby increasing their risk of fracture.

The analysis, which is published in the Journal of Bone and Mineral Research, included 54 trials involving 8747 individuals. Overall, no benefits of vitamin D over placebo were observed for improving muscle health. On the contrary, vitamin D appeared to have detrimental effects in terms of increased time spent performing what’s called the Timed Up and Go test, a decrease in maximum strength at knee flexion, and a tendency towards a reduced score of the Short Physical Performance Battery.

“Care should be taken recommending vitamin D supplementation to improve muscle strength and function in people with normal or only slightly impaired vitamin D status,” said lead author Lise Sofie Bislev, MD, PhD, of Aarhus University Hospital, in Denmark. “We need to study further whether it may benefit muscles in those with severe vitamin D deficiency, however.”

Source: Wiley