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Mutations in Muscle Stem Cells Cause Weakness During Aging

In a new study published in Nature Communications, Swedish researchers report that genetic mutations in muscle stem cells can prevent cell regeneration. The discovery by researchers at the Karolinska Institutet may mean new medications and treatments to help build stronger muscles even later in life.

Age affects every part of the body - skin quality changes, the hair thins and waistlines thicken. Another thing that occurs as a consequence of aging is the decline of muscular function.

"As we age, our muscles weaken, which makes things like standing, walking, lifting, turning and gripping difficult," said Dr. Bill Johnson, a stem cell physician in Dallas, Texas.

Weak muscles can mean the potential for injury, including muscle tears, strains and injuries that happen because of trauma or overuse.

Musculoskeletal injuries can be painful and, for many individuals, take a long time to heal. Extended healing is especially true for older populations who do not produce muscle tissue as quickly as younger people.

"A muscle tear at an advanced age can mean months or even longer of inactivity and rest while it heals," Johnson said.

Long periods of rest may be detrimental to the health of older individuals.

"Sitting for long periods of time isn't healthy, particularly for older people. Muscles atrophy more quickly, and the risk of injury becomes greater," Johnson said.

While researchers have known that aging negatively impacts muscle function and that the quantity and activity of muscle stem cells also decreased, they did not know until now what exactly caused these things to happen.

The reason they found was higher numbers of mutations in muscle stem cells.

During their research, they analyzed muscle tissue collected from participants in collaboration with the Unit for Clinical Physiology at Karolinska University Hospital.

Their findings revealed that an otherwise healthy 70-year-old had more than 1,000 mutations in every stem cell in an analyzed muscle. They also found that the variations did not occur randomly and that some areas were more protected than others.

Cell mutations happen during cell division. Protected areas tended to be areas that were critical for cell function or survival.

The study authors also found that this protection decreases with age. They hope to be able to reduce or reverse this situation with new medications. They also hope to develop exercises that would be appropriate for aging populations with muscle decline.

The Swedish study was performed using single stem cells that were proliferated in a lab to have enough DNA for sequencing.

The researchers also want to investigate the impact of exercise on muscle stem cell mutations, and if working out from an early age can help to reduce the number of affected stem cells or if exercising contributes to an increased number of mutated cells.

While the Swedish researchers are hoping for new drug interventions for muscle weakness, others, like Johnson, are helping to support muscles and heal muscle injuries with fat stem cell therapy.

"The stem cells that create fat and those that create muscle are the same types of stem cells: mesenchymal stem cells. Fat stem cell therapy can help repair muscle injuries and strengthen muscles," Johnson said.

In addition to declining muscle strength, another consequence of aging is the development of osteoarthritis, also known as degenerative joint disease.

"Osteoarthritis develops when the connective tissue that cushions the joints breaks down," Johnson said.

When this happens, bone rubs against bone, making movements very painful and limiting.

Fat stem cell therapy can also help reduce the pain of osteoarthritis by repairing damaged connective tissue and returning cushion to the joints. This can make a significant difference for patients affected by the condition.

"Osteoarthritis commonly affects the knees, hips, back and wrists. When it hurts to move these joints, most people stop moving. When this happens, a healthy person can quickly decline," Johnson said.


Karolinska Institutet. "Stem cell study may result in stronger muscles in old age." ScienceDaily. ScienceDaily, 23 February 2018.

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