Energy & Environment

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08 April 2009
Scientists Find Humans Grow New Heart Muscle

By Daniel Gorelick
Staff Writer

Washington — Scientists are using measurements of the radioactive carbon produced by Cold War-era nuclear bomb tests to prove adult humans replace heart muscle.

The findings, published in the April 3 issue of Science magazine, address the long-standing question of whether heart muscle cells divide after birth and suggest that stimulating heart muscle regeneration is a viable strategy for combating heart disease.

“The loss of heart cells after, say, a heart attack often leads to impaired cardiac function,” said study leader Jonas Frisén of the Karolinska Institute in Stockholm. “This new finding that heart cells can be replaced motivates further research into ways of stimulating the renewal mechanism to replace the cells that have been lost.”

Globally, heart disease is the leading cause of death, representing 30 percent of all deaths in 2005, according to the World Health Organization. More than a third of those deaths were caused by heart attacks. (See “Heart Disease a Leading Cause of Death Worldwide.”)

Frisén and colleagues estimate that about 1 percent of heart muscle cells divide annually at age 25, dropping to less than half that amount at age 75.

MEASURING CARBON IN DNA

Above-ground tests of nuclear weapons during the Cold War caused a sharp increase in atmospheric concentrations of carbon-14, a form of carbon that is normally present in trace amounts, according to the study. (The number 14 refers to the mass of this form of carbon atom; carbon-12 accounts for about 99 percent of all carbon.)

Even though tests were usually conducted in remote locations, the fallout spread around the world. Carbon-14, like carbon-12, reacts with oxygen to form carbon dioxide, which is incorporated into plants by photosynthesis.

“Humans eat plants and animals that live off plants, so the carbon-14 concentration in the human body mirrors that in the atmosphere at any given time,” the authors wrote.

The worldwide spike in carbon-14 ended in 1963, when the Limited Nuclear Test Ban Treaty prohibited nuclear explosions in the atmosphere, underwater or in outer space. Atmospheric carbon-14 levels dropped exponentially as carbon-14 diffused out of the atmosphere.

Carbon-14 ultimately wound up in human DNA, which remains intact after a cell divides.

By measuring the amount of carbon-14 incorporated into DNA and comparing that with the amount of carbon-14 in the atmosphere, scientists were able to determine the age of heart cells and show that a small percentage was younger than the age of the human.

Study co-author Bruce Buchholz, a physicist at Lawrence Livermore National Laboratory in California, used a technique called mass spectrometry to determine carbon-14 levels in human tissue. Mass spectrometry is able to distinguish the small difference in mass between carbon-14 and other forms of carbon, such as carbon-12.

Frisén and Australian scientist Kirsty L. Spalding first used carbon-14 levels to date human tissue in 2005. Since then, their method has been used to measure the age of cells throughout the body. A 2008 study showed the number of fat cells remains relatively constant in adults, suggesting that increasing fat mass is due to increases in the size, not the number, of fat cells.

A HEART DIVIDED

Muscle cells in the heart divide before birth. Other types of cells continue to divide after birth, but muscle cell division slows dramatically. Most of the subsequent increase in heart size comes from an increase in muscle cell size, not in the number of cells.

To complicate matters, the DNA in heart muscle cells often replicates in the absence of cell division, leading to cells that contain multiple copies of DNA. Frisén and colleagues painstakingly sorted heart muscle and identified cells containing the normal amount of DNA, ensuring the accuracy of their carbon-14 analysis.

After a heart attack, heart muscle is lost and replaced by scar tissue. Frisén and colleagues hope that their study will spur efforts to increase the rate of cell division.

Whether cell division occurs in response to injury is unknown. The source of the new heart muscle cells also remains a mystery. Do they arise from old muscle cells that suddenly divide, or from an undiscovered population of stem cells in or near the heart?

Answering these questions could bring researchers one step closer to mitigating the effects of heart failure.

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