The liver has a unique ability to regenerate after damage. However, it was not known whether this ability decreases as we age. International scientists led by Dr. Olaf Bergmann of the Dresden Center for Regenerative Therapies (CRTD) at TU Dresden used a technique known as retrospective radiocarbon birth dating to determine the age of the human liver. They showed that, regardless of a person’s age, the liver is always on average less than three years old. The results show that aging does not affect liver renewal, making the liver an organ that replaces its cells just as well in young and old. The interdisciplinary study was published in the journal Cell Systems.
The liver is an essential organ that is responsible for removing toxins from our body. Because he is constantly dealing with toxic substances, he is likely to be injured regularly. To overcome this, the liver has a unique ability between organs to regenerate after damage. Because much of the body’s ability to heal and regenerate decreases as we age, scientists have wondered if the liver’s ability to renew itself also decreases with age.
The nature of liver renewal in humans also remained a mystery. Animal models gave contradictory answers. “Some studies pointed to the possibility of liver cells being long-lived while others showed a constant rotation. We were clear that if we want to know what happens in humans, we need to find a way to directly assess age. of the human being. liver cells “, says Dr. Olaf Bergmann, leader of the research group of the Center for Regenerative Therapies Dresden (CRTD) of the TU Dresden.
The human liver is still a young organ
The interdisciplinary team of biologists, physicists, mathematicians and clinicians led by Dr. Bergmann analyzed the livers of multiple individuals who died between the ages of 20 and 84. Surprisingly, the team showed that the liver cells of all subjects were about the same age.
“It doesn’t matter if you’re 20 or 84, your liver stays on average for just under three years,” says Dr. Bergmann. The results show that the adjustment of liver mass to the needs of the body is closely regulated by the constant replacement of liver cells and that this process is maintained even in the elderly. This ongoing liver cell replacement is important for various aspects of liver regeneration and cancer formation.
Liver cells with more DNA are renewed less
However, not all cells in our liver are so young. A fraction of cells can live up to 10 years before being renewed. This subpopulation of liver cells carries more DNA than typical cells. “Most of our cells have two sets of chromosomes, but some cells accumulate more DNA as they age. In the end, those cells can carry four, eight, or even more sets of chromosomes.” explains Dr. Bergmann.
“When we compared typical liver cells with the richest DNA cells, we found fundamental differences in their renewal. Typical cells are renewed about once a year, while cells are renewed. DNA-rich cells can reside in the liver for up to a decade, “says Dr. Bergmann. “As this fraction gradually increases with age, this could be a protective mechanism to protect us from the accumulation of harmful mutations. We need to find out if there are similar mechanisms in chronic liver disease, which in some cases can become cancer “.
Lessons from the nuclear fall
Determining the biological age of human cells is a massive technical challenge, as the methods commonly used in animal models cannot be applied to humans.
Dr.’s group Bergmann specializes in retrospective radiocarbon birth dating and uses the technique to assess the biological age of human tissues. Carbon is a chemical element that is ubiquitous and forms the backbone of life on Earth. Radiocarbon is one of the different types of carbon. It appears naturally in the atmosphere. Plants incorporate it through photosynthesis, in the same way as typical carbon, and transmit it to animals and humans. Radiocarbon is weakly radioactive and unstable. These features are used in archeology to determine the age of ancient specimens.
“Archaeologists have used radiocarbon decomposition successfully for many years to assess the age of specimens, one example being the dating of the Turin shroud,” says Dr. Bergmann. “Radioactive decay of radiocarbon is very slow. It provides enough resolution for archaeologists, but it is not useful in determining the age of human cells. However, we can still take advantage of radiocarbon in our research.”
Nuclear ground tests conducted in the 1950s introduced massive amounts of radiocarbon into the atmosphere, plants, and animals. As a result, cells formed during this period have higher amounts of radiocarbon in their DNA.
Following the official ban on ground-based nuclear testing in 1963, the amounts of atmospheric radiocarbon began to decline, as did the amounts of radiocarbon incorporated into animal DNA. Atmospheric and cellular radiocarbon values correspond very well.
“Although these are insignificant amounts that are not harmful, we can detect and measure them in tissue samples. By comparing the values with atmospheric radiocarbon levels, we can retrospectively establish the age of the cells. “, explains Dr. Bergmann.
Unmatched insights directly from the source
The Bergmann Group also explores the mechanisms that drive the regeneration of other tissues considered static, such as the brain or heart. The team has previously used its experience in retrospective radiocarbon birth dating to show that the formation of new brain and heart cells is not limited to prenatal time but continues throughout life. The group is currently investigating whether new muscle cells in the human heart can still be generated in people with chronic heart disease.
“Our research shows that studying cell renewal directly in humans is technically very difficult, but it can provide an incomparable insight into the underlying cellular and molecular mechanisms of human organ regeneration,” concludes Dr. Bergmann.
Source:
Dresden Technical University
Magazine reference:
Heinke, P., et al. (2022) Diploid hepatocytes drive physiological renewal of the liver in adult humans. Cellular systems. doi.org/10.1016/j.cels.2022.05.001.