Why do aged muscles heal slowly?

July 5, 2016, Carnegie Institution for Science
A normal muscle compared to a muscle lacking b1-integrin courtesy of Chen-Ming Fan and Michelle Rozo.

As we age, the function and regenerative abilities of skeletal muscles deteriorate, which means it is difficult for the elderly to recover from injury or surgery. New work from Carnegie's Michelle Rozo, Liangji Li, and Chen-Ming Fan demonstrates that a protein called b1-integrin is crucial for muscle regeneration. Their findings, published by Nature Medicine, provide a promising target for therapeutic intervention to combat muscle aging or disease.

Muscle are the primary source of after injury. These specialized lie dormant in the tissue—off to the side of the individual , which is why they were originally dubbed satellite cells. When muscle fibers are damaged, they activate and proliferate. Most of the new cells go on to make new muscle fibers and restore . Some return to dormancy, which allows the muscle to keep repairing itself over and over again.

Rozo, the lead author, determined that the function of integrins (or, more specifically, the protein called β1-integrin) is absolutely crucial for maintaining the cycle of hibernation, activation, proliferation, and then return to hibernation, in muscle stem cells. Integrins are proteins that 'integrate' the outside to the inside of the cell, providing a connection to the immediate external environment, and without them, almost every stage of the regenerative process is disrupted.

The team theorized that defects in β1-integrin likely contribute to phenomena like aging, which is associated with reduced muscle stem cell function and decreased quantities of muscle stem cells. This means that healing after injury or surgery is very slow, which can cause a long period of immobility and an accompanying loss of .

"Inefficient muscular healing in the elderly is a significant clinical problem and therapeutic approaches are much needed, especially given the aging population–and I am including myself in this population," Fan explained. "Finding a way to target muscle stem cells could greatly improve muscle renewal in older individuals."

Rozo and Li determined that the function of β1-integrin is diminished in aged muscle stem cells. Furthermore, when they artificially activated integrin in mice with aged muscles, their regenerative abilities were restored to youthful levels. Importantly, improvement in regeneration, strength, and function were also seen when this treatment was applied to animals with muscular dystrophy, underscoring its potential importance for the treatment of muscle disorders.

Muscle stem cells use b1-integrin to interact with many other proteins in the muscle external environment. Among these many proteins, they found a clue that one called fibronectin might be most relevant. To connect b1-integrin to fibronectin, they teamed up with another group led by scientists from the Nestlé Institute of Health Sciences, in addition to researchers from the EPFL EDBB Doctoral Program, the Leibniz Institute for Age Research, the Ottawa Hospital Research Institute, and the Max Planck Institute of Biochemistry.

They discovered that aged muscles contain substantially reduced levels of fibronectin compared to young muscles. Like b1-integrin, eliminating fibronectin from young muscles makes them appear as if they were old, and restoring fibronectin to aged muscle tissue restores muscle regeneration to youthful levels. Their joint efforts demonstrated a strong link between b1-integrin, fibronectin and muscle , which is the subject of a second paper, also published by Nature Medicine in the same issue.

"Taken together, our results show that aged with compromised b1-integrin activity and aged muscles with insufficient amount of fibronectin both root causes of muscle aging. This makes b1-integrin and fibronectin very promising therapeutic targets," Fan said.

Explore further: New method to grow and transplant muscle stem cells holds promise for treatment of MD

More information: Michelle Rozo et al. Targeting β1-integrin signaling enhances regeneration in aged and dystrophic muscle in mice, Nature Medicine (2016). DOI: 10.1038/nm.4116

Laura Lukjanenko et al. Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice, Nature Medicine (2016). DOI: 10.1038/nm.4126

Related Stories

New method to grow and transplant muscle stem cells holds promise for treatment of MD

June 28, 2016
Satellite cells are stem cells found in skeletal muscles. While transplantation of such muscle stem cells can be a potent therapy for degenerative muscle diseases such as Duchenne muscular dystrophy, these cells tend to lose ...

Scientist identify first steps in muscle regeneration

May 20, 2016
Scientists from Monash University's Australian Regenerative Medicine Institute ARMI have found the first real evidence of how muscles may be triggered to regenerate or heal when damaged. The research could open the way to ...

Stem cell therapy as a potential treatment for severe burns patients

June 27, 2016
Scientists have discovered a new way to potentially treat muscle regeneration in patients with severe burns according to a study published today in The Journal of Physiology.

Exercise may have therapeutic potential for expediting muscle repair in older populations

June 17, 2016
Here's another reason why you should hit the gym regularly as you grow older: A new report appearing online in The FASEB Journal shows that regular exercise plays a critical role in helping muscles repair themselves as quickly ...

At the right place at the right time—new insights into muscle stem cells

September 17, 2012
Muscles have a pool of stem cells which provides a source for muscle growth and for regeneration of injured muscles. The stem cells must reside in special niches of the muscle for efficient growth and repair.

Recommended for you

New insight into stem cell behaviour highlights therapeutic target for cancer treatment

December 12, 2018
Research led by the University of Plymouth and Technische Universität Dresden has identified a new therapeutic target for cancer treatment and tissue regeneration – a protein called Prominin-1.

Study examines disruption of circadian rhythm as risk factor for diseases

December 11, 2018
USC scientists report that a novel time-keeping mechanism within liver cells that helps sustain key organ tasks can contribute to diseases when its natural rhythm is disrupted.

New light-based technology reveals how cells communicate in human disease

December 11, 2018
Scientists at the University of York have developed a new technique that uses light to understand how cells communicate in human disease.

Researchers explore new way of killing malaria in the liver

December 8, 2018
In the ongoing hunt for more effective weapons against malaria, international researchers said Thursday they are exploring a pathway that has until now been little studied—killing parasites in the liver, before the illness ...

Study may offer doctors a more effective way to treat neuroblastoma

December 7, 2018
A very large team of researchers, mostly from multiple institutions across Germany, has found what might be a better way to treat patients with neuroblastoma, a type of cancer. In their paper published in the journal Science, ...

Progress made in transplanting pig hearts into baboons

December 6, 2018
A large team of researchers from several institutions in Germany, Sweden, Switzerland and the U.S. has transplanted pig hearts into baboons and kept them alive for an extended period of time. In their paper published in the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.