Surprise! Your liver is just 3 years old, whether you're 20 or 84

You heard it right.

According to new research, the human liver remains young even while the rest of our bodies grow old. And on average, the organ is less than three years old, regardless of the person's age.

The liver, one of the largest and most important organs in a person's body, is in charge of clearing toxins. And because it constantly deals with toxic substances, it has a high chance of getting injured regularly. To overcome this, the liver has a distinct capability among organs to regenerate itself after damage.

"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," said Dr. Olaf Bergmann, molecular biologist and research group leader at the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden.

The research was published in Cell Systems.

Retrospective birth dating led to the result

An interdisciplinary team of biologists, physicists, mathematicians, and clinicians led by Bergmann analyzed the livers of multiple individuals who died at the ages of 20 and 84 years old. Much to their surprise, 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,” said Bergmann.

Now, determining the biological age of human cells is an enormous challenge, as techniques used in animal models cannot be applied to humans. 

The scientists used mathematical modeling and a technique called retrospective birth dating - which dates human cells based on levels of a carbon isotope that spiked in the atmosphere following mid-20th century nuclear testing - and found that liver renewal is unaffected as we grow old. 

The results showed that the 'adjustment of liver mass to the needs of the body is tightly regulated through the constant replacement of liver cells'. This particular liver cell replacement is essential for other aspects of liver regeneration and cancer formation. 

Not all liver cells are the same

However, not all liver cells are the same in terms of renewal. A small fraction of cells can live up to 10 years before renewing itself. This set of liver cells carries more DNA than the other 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," said Bergmann.

When the researchers compared typical liver cells with the cells richer in DNA, fundamental differences were found 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," said 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."

A crucial finding

The Bergmann group is also looking into the mechanisms that control the regeneration of other tissues, such as the brain or the heart. 

Previously, the team had used their expertise in retrospective radiocarbon birth dating to show that the formation of new brain and heart cells continues throughout life. 

Currently, the group is looking at new human heart muscle cells and if they can be generated in people with chronic heart disease.

“Our research 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,” added Bergmann.

These findings are imperative - the more we're aware of the organs in our body, the better we can get at finding out how to keep them away from disease.