Eroded Telomeres May Impair Heart Regeneration

Researchers in Spain have discovered that heart muscle cell telomeres are chipped away after birth, limiting their ability to proliferate and repair any damage

Zebrafish and newborns can repair heart tissue highly effectively, but this ability declines in humans early on in life – leaving harmful scar tissue following injury. Dysfunctional telomeres are already linked to a range of health conditions, and now research is suggesting they may be involved in cardiovascular health too. 

Researchers at the Spanish National Center for Cardiovascular Research in Madrid noted that much the same process happens in mice, with newborns gradually losing their regenerative ability. They theorized this might have something to do with telomere loss, as shortened telomere caps impose a block on cell division and therefore regeneration. 

What did they find? 

They discovered that telomere lengths rapidly declined in just the 1st week after birth, coinciding with a loss of the crucial enzyme telomerase, which maintains telomere length. This shortening activated a DNA damage response, leading to an imposed halt on cell division and proliferation. 

Telomerase deficient tissue (right) displays poor regenerative capacity just 1 day after birth, producing larger fibrotic deposition following damage (blue). Credit: Aix et al., 2016

Indeed, in telomerase deficient mice they found that after a cardiovascular injury 1 day after birth, deficient mice were unable to repair the damage, whereas wild type mice kept their regenerative capacity for longer, in conjunction with their telomeres (although this was eroded within the week instead). When the team knocked out a cell cycle inhibitor triggered by telomere loss in normal mice, they found they retained their regenerative ability for longer. 

This means that telomere erosion could actually play a role in impairing heart repair, and that telomerase induction may be a novel strategy following a heart attack for example. This is still only a theory, but the researchers are developing another mice model with increased telomerase expression to explore the question further. 

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