 Heart disease is the leading cause of death worldwide. While people have benefited greatly from advances in drugs and surgery, one glaring problem remains. Unlike the cells that make up our other muscles, once heart cells are gone, they simply can't be regenerated. That is, unless you were just born. Studies show that muscle cells in the hearts of newborn mice, rabbits, and even humans can go on dividing for up to days after birth. And now, in what could be a new world record, scientists have recorded signs of regeneration beyond two weeks after birth in the South American gray, short-tailed opossum. Their ability to replicate this feat in mice could point to new ways of healing the hearts of humans with cardiovascular disease. The experiments that led to these results were carried out by Wataru Komura and colleagues at the Riken Center for Biosystems Dynamics Research in Japan. The team chose the opossum because unlike other mammals, marsupials, which also include koalas and kangaroos, are born underdeveloped. That means after birth, many of their internal organs continue to grow, including their hearts. The team figured that if this growth were linked to the continued division of heart muscle cells, then it might be possible for marsupial hearts to regenerate after injury. And that's precisely what they found. Opossum hearts continue to grow beyond 14 days after birth. In fact, the hearts of two-week-old opossums resembled the hearts of newborn mice who were only a day old. Experimentally induced heart damage at this age was found to be repaired within one month, indicating that as long as heart cells continue to divide, the heart can be repaired. The next step was figuring out what makes this possible in opossums, but not mice. Comparisons of gene expression between the two creatures revealed one common factor, the energy-regulating enzyme AMPK. Activation of AMPK in both mice and opossums coincided with the stoppage of cell division in heart muscle. Naturally, the team wondered whether inhibiting AMPK could extend the period during which heart regeneration is possible. When they injected newborn mice with AMPK inhibitors, the team found that hearts that were experimentally damaged one week after birth could regenerate and regain normal function with minimal scarring. In essence, the researchers were able to use what they learned from marsupials and induce heart regeneration in a regular mammal. The team is now interested in determining what triggers AMPK expression at birth in mice, but not in opossums and exploring what makes the marsupial heart so special. Their findings, the team says, could lead to therapies that could induce heart regeneration in adult humans.