Genetic switch controls body's tissue repair system

February 18, 2014 by Mohit Kumar Jolly, The Conversation
Those days need not remain in photographs. Credit: carlos-smith

It is a sad fact that old age brings diseases. Many may not be life-threatening, but they make life less fun. One such condition is sarcopenia, which causes the loss of muscle mass and strength, and it is the reason why some old people suffer from loss of stamina, difficulty in walking and heavy breathing.

Sadly there is no treatment for the condition, except for exercise, which only becomes more cumbersome with age. Understanding sarcopenia, then, is crucial to developing new therapies. Now, in a paper published in Nature, scientists have identified the mechanism for this irreversible wear and tear of muscles as one ages.

Our body is made of trillions of cells. Most organs – including the brain, liver, heart, gut and blood vessels – have known as adult , which maintain and repair the organ. The resting state of these cells is "quiescent" – that is, they divide only when required for , unlike that keep dividing throughout their lifetimes. When these are removed or they stop functioning, the body's repair system stops too. This usually happens with age, leading to degenerative diseases such as sarcopenia.

Now researchers at Pompeu Fabra University, Bellvitge Biomedical Research Institute, and CNIC in Spain have deciphered how stem cells stop working, at least for those found in muscles. By comparing the genes that are turned "on" in of mice – who act as proxy for humans – the researchers show that the cells of older mice undergo irreversible changes that make them lose their quiescence stage, whereas younger mice are spared the change. Because of this, the potential of muscle stem cells in older mice to self-renew when required is lost too. Instead they switch to being "senescent", the state in which they cannot divide any more.

Normally senescence is useful. Regardless of how old you are, millions of your body's cells become senescent every day. One of the functions of senescence is to keep a check on uncontrolled growth of that may become cancerous. But senescence becomes more common as we age. And in the case of old people, senescence among stem cells is halting the tissue repair system.

To be sure that it wasn't the environment causing this response, the researchers extracted muscle stem cells from older mice and implanted them in damaged tissue of younger mice. As expected, the geriatric cells did not repair the tissue, showing that their state was irreversible.

But how exactly do the cells undergo these changes? The researchers found that in old muscle stem cells, the key gene that controls senescence, p16INK4a, is overexpressed – that is, it is switched "on" more than normal. When this gene was not allowed to be expressed, the old cells responded to tissue injury, and replenished the cell population, thereby returning to the quiescence state. The researchers also show that young muscle stem cells repress the production of the gene, which allows them to carry out repair work whenever needed.

The hope would be that, if p16INK4a can be selectively silenced, then this discovery would lead to a treatment for restarting the tissue repair system in old cells. While targeting specific genes in specific cells is not easy, remaining younger and healthier for longer may not always remain that hard.

Explore further: Researchers rejuvenate stem cell population from elderly mice, enabling muscle recovery

More information: "Geriatric muscle stem cells switch reversible quiescence into senescence." Pedro Sousa-Victor,Susana Gutarra, Laura García-Prat, Javier Rodriguez-Ubreva, Laura Ortet, Vanessa Ruiz-Bonilla, Mercè Jardí, Esteban Ballestar, Susana González, Antonio L. Serrano, Eusebio Perdiguero, Pura Muñoz-Cánoves. Nature (2014) DOI: 10.1038/nature13013

Related Stories

Researchers rejuvenate stem cell population from elderly mice, enabling muscle recovery

February 16, 2014
Researchers at the Stanford University School of Medicine have pinpointed why normal aging is accompanied by a diminished ability to regain strength and mobility after muscle injury: Over time, stem cells within muscle tissues ...

Stem cell transplant repairs damaged gut in mouse model of inflammatory bowel disease

October 17, 2013
A source of gut stem cells that can repair a type of inflammatory bowel disease when transplanted into mice has been identified by researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute at ...

Different cellular mechanisms behind regenerated body parts

November 21, 2013
Scientists at Karolinska Institutet in Sweden have discovered that two separate species of salamander differ in the way their muscles grow back in lost body parts. Their findings on the species-specific solutions, published ...

A step closer to muscle regeneration

December 10, 2013
(Medical Xpress)—Muscle cell therapy to treat some degenerative diseases, including Muscular Dystrophy, could be a more realistic clinical possibility, now that scientists have found a way to isolate muscle cells from embryonic ...

Stem cells overcome damage in other cells by exporting mitochondria

January 16, 2014
A research team has identified a protein that increases the transfer of mitochondria from mesenchymal stem cells to lung cells. In work published in The EMBO Journal, the researchers reveal that the delivery of mitochondria ...

New research implicates immune system cells in muscle healing

December 6, 2013
Scientists have found that cells known primarily for tempering immune response also exist in injured muscle tissue, an unexpected role for regulatory T cells.

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.


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.