As we all know, liver is one of the very important "five internal organs", which is responsible for removing toxins from our body. Due to its constant interaction with toxic substances, the liver is always at high risk. Fortunately, it has a unique ability to regenerate itself after damage. This is attributed to the proliferative ability of liver cells .
As we all know, as we age, most of our organs will gradually age. How does the liver change during this process? Will liver parenchymal cells be constantly renewed? Or will they be long-lived cells like cardiomyocytes and neurons, able to maintain their structural and functional integrity for decades? As of now, this remains a mystery.
Past studies based on animal models have given conflicting results: Some studies estimated the age of liver cells in rodents at between 200 and 400 days, pointing to the possibility of liver cell longevity; Will be updated continuously.
Obviously, the above conclusion casts another layer of veil on the mystery of human liver cell renewal.
On May 31, 2022, in a new study published in the Cell sub-journal "Cell Systems" , an international research team led by TU Dresden in Germany solved this long-standing mystery. This study tells us that the liver is an organ that “remains young forever.”
Determining the biological age of human cells has been a huge technical challenge because methods typically used in animal models are not applicable to humans. Therefore, so far, the scientific community still lacks a comprehensive exploration of the dynamic characteristics of human liver cell renewal.
In the new study, an interdisciplinary team of biologists, physicists, mathematicians and clinicians found a way to directly assess the age of human liver cells. They provide a comprehensive model of human liver cell turnover and their age distribution through retrospective radiocarbon birth dating and mathematical modeling.
The team analyzed the livers of multiple people who died between the ages of 20 and 84. Surprisingly, the age of the liver cells of all deceased patients was almost the same as that of . In other words, whether you are 20 years old or 84 years old, the average lifespan of the liver is less than 3 years.
research results show that liver mass demands on the body are tightly regulated through constant replacement of liver cells, a process that can be maintained even in old age. This ongoing liver cell turnover is important for all aspects of liver regeneration and cancer development.
However, not all cells in the liver stay so young. A small percentage of cells can survive for 10 years before renewing themselves. This subset of liver cells carries more DNA than typical liver cells.
Dr. Olaf Bergmann, corresponding author of the study and head of the Dresden Center for Regenerative Therapy at the University of Dresden, explained: "Most of our cells have two sets of chromosomes, but some cells accumulate more DNA as they age. "Eventually, these cells can carry four, eight or even more sets of chromosomes."
When comparing typical liver cells with those that contain more DNA, the researchers found fundamental differences in how they self-renew. Typical cells are replaced about once a year; cells with more DNA can survive in the liver for up to ten years. This proportion gradually increases with age.
Bergmann said: "This may be a protective mechanism that prevents us from accumulating harmful mutations. As a next step, we want to confirm whether a similar mechanism exists in chronic liver diseases, because in some cases these diseases may transform into cancer."
Bergmann "Determining these signatures of adult hepatocyte turnover is important because this will lead to a better understanding of the development of age-related diseases and liver cancer," said .
The team also explored the mechanisms that drive regeneration in other tissues considered static, such as the brain or heart. The team has previously used their expertise in retrospective radiocarbon birth dating to show that the formation of new brain and heart cells is not limited to the prenatal period but occurs throughout life. Currently, they are studying whether patients with chronic heart disease can generate new human heart muscle cells.
Bergmann concluded: "Our study shows that studying cell renewal directly in humans is technically very challenging, but it can provide unparalleled insights into the underlying cellular and molecular mechanisms of human organ regeneration."
Paper link:
https: //doi.org/10.1016/j.cels.2022.05.001
