Studies show that aging does not affect liver regeneration

The liver has a unique ability to regenerate after injury. However, it was unclear whether this ability would decline with age. International scientists, led by Dr. Olav Bergman of the Dresden Center for Regenerative Therapy (CRTD), used a technique known as retrocarbon dating to determine the age of the human liver. They showed that the liver was always under 3 years old on average, regardless of the person’s age. The results show that aging does not affect liver regeneration, which is an organ that replaces cells alike, young and old. The interdisciplinary study was published in the journal Cell Systems.

The liver is an important organ that helps remove toxins from our body. Since we are always dealing with toxic substances, we may be injured on a regular basis. To overcome this, the liver has a unique ability within the organ to regenerate itself after injury. As we grow older, scientists suspect that the ability of the liver to regenerate also declines with age, as much of the body’s ability to heal and regenerate itself diminishes.

The nature of human liver regeneration also remained a mystery. Animal models provided inconsistent answers. “Some studies point out that liver cells may have a long lifespan, while others show a constant turnover. If you want to know what’s happening in humans, how to directly assess human age? It was clear that we needed to find hepatocytes, “said Dr. Olavbergmann, research group leader at the Center for Regenerative Therapy (CRTD) in Dresden.

The human liver is still a young organ

An interdisciplinary team of biologists, physicists, mathematicians, and clinicians led by Dr. Bergman analyzed the livers of multiple individuals who died between the ages of 20 and 84. Surprisingly, the team showed that the hepatocytes of all subjects were more or less the same age.

“Whether you’re 20 or 84, your liver remains on average just under 3 years old,” explains Dr. Bergmann. The results show that the regulation of liver mass for the body’s needs is tightly regulated by the constant exchange of liver cells, and this process is maintained in the elderly. This ongoing hepatocellular replacement is important for various aspects of liver regeneration and cancer formation.

Hepatocytes with a lot of DNA have less renewal

But not all cells in our liver are so young. Some cells can live up to 10 years before renewing themselves. This subpopulation of hepatocytes carries more DNA than typical cells. “Most of our cells have two sets of chromosomes, but some cells accumulate more DNA as they age. Ultimately, such cells are 4, 8, or so. It can carry the above set of chromosomes, “explains Dr. Bergman.

Comparing typical hepatocytes with DNA-rich cells showed a fundamental difference in their regeneration. Typical cells are renewed about once a year, but DNA-rich cells can be present in the liver for up to 10 years. This percentage may increase gradually with age, so this may be a protective mechanism that protects us from the accumulation of harmful mutations. Chronic liver disease has a similar mechanism, and in some cases it is necessary to find out if it can lead to cancer. “

Dresden TU Dresden Regenerative Therapy Center (CRTD), Dr. Olaf Bergman

Lessons from fallout

Determining the biological age of human cells is a major technical challenge, as the methods commonly used in animal models are not applicable to humans.

Dr. Bergman’s group specializes in retroactive radiocarbon dating and uses this technique to assess the biological age of human tissue. Carbon is an ubiquitous chemical element that forms the backbone of life on Earth. Radiocarbon is one of many types of carbon. Appears naturally in the atmosphere. Plants take it up by photosynthesis and pass it on to animals and humans, just like normal carbon. Radiocarbon is weak and unstable. These features are used in archeology to date ancient samples.

“Archaeologists have used radiocarbon dating for many years to date specimens, one example of which is the dating of the Shroud of Turin,” says Dr. Bergman. “Radioactive decay of radiocarbon is very slow. It provides archaeologists with sufficient resolution, but it does not help determine the age of human cells. Still, in our study we have radiocarbon. available.”

Ground-based nuclear tests conducted in the 1950s introduced large amounts of radiocarbon into the atmosphere, plants, and animals. As a result, cells formed during this period contain a large amount of radiocarbon in their DNA.

After the official ban on ground-based nuclear tests in 1963, the amount of radiocarbon in the atmosphere began to decline, and so did the amount of radiocarbon incorporated into animal DNA. The values ​​of radiocarbon in the atmosphere and cells correspond very well to each other.

“These are very small amounts that are not harmful, but can be detected and measured in tissue samples. By comparing the values ​​to the levels of radiocarbon in the atmosphere, we can retroactively confirm the age of the cells,” Bergman said. The doctor explains.

Unmatched insights directly from the source

The Bergman Group is also investigating mechanisms that promote the regeneration of other tissues that are considered static, such as the brain and heart. The team previously used their expertise in retrocarbon dating to show that the formation of new brain and heart cells is not limited to prenatal time and lasts a lifetime. Currently, this group is investigating whether new human cardiomyocytes can still be produced in people with chronic heart disease.

“Our research shows that direct study of human cell regeneration is technically very difficult, but it is unmatched to the cellular and molecular mechanisms underlying human organ regeneration. We can provide insights, “Dr. Bergman concludes.