The liver has a unique ability to regenerate after damage. However, it was unknown whether this ability decreases as we age. International scientists led by Dr. Olaf Bergmann at the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden used a technique known as retrospective radiocarbon birth dating to determine the age of the human liver.
They showed that no matter the person's age, the liver is always on average less than three years old. The results demonstrate that aging does not influence liver renewal, making the liver an organ that replaces its cells equally well in young and old people. The interdisciplinary study was published in Cell Systems.
Human liver is composed of cells with different amounts of DNA.
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The liver is an essential organ that takes care of clearing toxins in our bodies. Because it constantly deals with toxic substances, it is likely to be regularly injured. To overcome this, the liver has a unique capacity among organs to regenerate itself after damage. Because a lot of the body’s ability to heal itself and regenerate decreases as we age, scientists were wondering if the liver’s capacity to renew also diminishes with age.
The nature of liver renewal in humans also remained a mystery. The animal models provided contradictory answers. "Some studies pointed to the possibility that liver cells are long-lived while others showed a constant turnover. It was clear to us that if we want to know what happens in humans, we need to find a way to directly assess the age of human liver cells," says Dr. Olaf Bergmann, research group leader at the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden.
The interdisciplinary team of biologists, physicists, mathematicians, and clinicians led by Dr. Bergmann analyzed the livers of multiple individuals who died at ages between 20 and 84 years old. Surprisingly, the team showed that the liver cells of all subjects were more or less the same age.
"No matter if you are 20 or 84, your liver stays on average just under three years old," explains Dr. Bergmann. The results show that the adjustment of liver mass to the needs of the body is tightly regulated through the constant replacement of liver cells and that this process is maintained even in older people. This ongoing liver cell replacement is important for various aspects of liver regeneration and cancer formation.
However, not all the cells in our liver are that young. A fraction of cells can live up to 10 years before renewing itself. This subpopulation of liver cells carries more DNA than the typical cells. "Most of our cells have two sets of chromosomes, but some cells accumulate more DNA as they age. In the end, such cells can carry four, eight, or even more sets of chromosomes," explains Dr. Bergmann.
"When we compared typical liver cells with the cells richer in DNA, we found fundamental differences in their renewal. Typical cells renew approximately once a year, while the cells richer in DNA 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 that safeguards us from accumulating harmful mutations. We need to find out if there are similar mechanisms in chronic liver disease, which in some cases can turn into cancer."