Mouse study links heart regeneration to telomere length

May 30, 2016, Rockefeller University Press
Telomerase-deficient mice undergo premature telomere shortening, and so, unlike wild-type mice, they are unable to regenerate damaged heart tissue even at one day old. 28 days after injury, telomerase-deficient heart tissue (right) has larger fibrotic regions (blue) compared with wild-type myocardium (left). Credit: Aix et al., 2016

Researchers at the Spanish National Center for Cardiovascular Research have discovered that the ends of heart muscle cell chromosomes rapidly erode after birth, limiting the cells' ability to proliferate and replace damaged heart tissue. The study, "Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation," which will be published online May 30, 2016 in The Journal of Cell Biology, suggests potential new interventions to boost the heart's capacity to repair itself after a heart attack.

Newborn babies can repair injured myocardium, but, in adults, heart attacks cause permanent damage, often leading to heart failure and death. Newborn mice can also regenerate damaged heart tissue. Their heart muscle cells, or cardiomyocytes, can proliferate and repair the heart in the first week after birth, but this is lost as the mice grow older and the majority of their cardiomyocytes withdraw from the .

Ignacio Flores and colleagues at the Spanish National Center for Cardiovascular Research (CNIC) in Madrid wondered whether the cause of this cell cycle arrest might involve , repetitive DNA sequences that protect the ends of chromosomes. If telomeres grow too short—due, for example, to a loss of the telomere-extending telomerase enzyme—cells can mistake chromosome ends for segments of damaged DNA, leading to the activation of a checkpoint that arrests the cell cycle.

Flores and colleagues therefore examined the length of telomeres in newborn mouse cardiomyocytes and found that the telomeres rapidly eroded in the first week after birth. This erosion coincided with a decrease in telomerase expression and was accompanied by the activation of the DNA damage response and a cell cycle inhibitor called p21.

Telomerase-deficient mice have shorter telomeres than wild-type animals, and, the researchers discovered, their cardiomyocytes already begin to stop proliferating one day after birth. When Flores and colleagues injured the hearts of one-day-old mice, telomerase-deficient cardiomyocytes failed to proliferate or regenerate the injured myocardium. In contrast, wild-type cardiomyocytes were able to proliferate and replace the damaged tissue.

They also found that knocking out the cell cycle inhibitor p21 extended the regenerative capacity of cardiomyocytes, allowing one-week-old p21-deficient mice to repair damaged cardiac tissue much more effectively than week-old wild-type animals.

Maintaining the length of cardiomyocyte telomeres might therefore boost the regenerative capacity of adult cells, improving the recovery of cardiac tissue following a attack. "We are now developing telomerase overexpression mouse models to see if we can extend the regenerative window," says Flores.

Explore further: Macrophage population activates repair in murine heart attack model

More information: Aix et al. 2016. J. Cell Biol. DOI: 10.1083/jcb.201510091

Related Stories

Macrophage population activates repair in murine heart attack model

May 3, 2016
Following a heart attack, successful repair of damaged tissue can prevent cardiac rupture and other adverse outcomes. The ability to repair myocardial tissue depends on the activation of fibroblasts, which stimulate the formation ...

Muscles on-a-chip provide insight into cardiac stem cell therapies

February 8, 2016
Stem cell-derived heart muscle cells may fail to effectively replace damaged cardiac tissue because they don't contract strongly enough, according to a study in The Journal of Cell Biology. The study, "Coupling Primary and ...

A tool for isolating progenitor cells from human heart tissue could lead to heart repair

October 7, 2015
A*STAR researchers and colleagues have developed a method to isolate and expand human heart stem cells, also known as cardiac progenitor cells, which could have great potential for repairing injured heart tissue.

Researchers describe new approach to promote regeneration of heart tissue

March 18, 2015
The heart tissue of mammals has limited capacity to regenerate after an injury such as a heart attack, in part due to the inability to reactivate a cardiac muscle cell and proliferation program. Recent studies have indicated ...

Oxygen diminishes the heart's ability to regenerate, researchers discover

April 24, 2014
Scientific research at UT Southwestern Medical Center previously discovered that the newborn animal heart can heal itself completely, whereas the adult heart lacks this ability. New research by the same team today has revealed ...

Researchers treat heart attacks with new gene therapy based on telomerase enzyme

December 18, 2014
The enzyme telomerase repairs cell damage produced by ageing, and has been used successfully in therapies to lengthen the life of mice. Now it has been observed that it could also be used to cure illnesses related to the ...

Recommended for you

Scientists reverse aging-associated skin wrinkles and hair loss in a mouse model

July 20, 2018
Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed?

Enzyme identified as possible novel drug target for sickle cell disease, Thalassemia

July 19, 2018
Medical researchers have identified a key signaling protein that regulates hemoglobin production in red blood cells, offering a possible target for a future innovative drug to treat sickle cell disease (SCD). Experiments ...

Mice given metabolite succinate found to lose weight by turning up the heat

July 19, 2018
A team of researchers with members from institutions across the U.S. and Canada has found that giving the metabolite succinate to mice fed a high-fat diet prevented obesity. In their paper published in the journal Nature, ...

Supplement may ease the pain of sickle cell disease

July 19, 2018
(HealthDay)—An FDA-approved supplement reduces episodes of severe pain in people with sickle cell disease, a new clinical trial shows.

Scientists uncover DNA 'shield' with crucial roles in normal cell division

July 18, 2018
Scientists have made a major discovery about how cells repair broken strands of DNA that could have huge implications for the treatment of cancer.

Researchers develop novel bioengineering technique for personalized bone grafts

July 18, 2018
Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a new bone engineering technique called Segmental Additive Tissue Engineering (SATE). The technique, described in a paper published ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

betterexists
not rated yet May 30, 2016
REMOVE WINGS (NOT Feathers) on SOME BIRD; Regenerate after 3 Months.

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.