Using Mini-organs To Better Understand Aging

Under the microscope, it becomes clear how complex even a tiny model of the liver can be: Some structures resemble small bubbles. Between them run fine canaliculi through which bile components are transported toward a miniature bile duct.

Anna Dowbaj helped develop this complex organoid model, called an assembloid. Unlike earlier liver organoids, it does not consist of just one cell type. It combines hepatocytes, cholangiocytes, and supporting mesenchymal cells. This allows the model to recreate the architecture and key functions of an important region of the liver more accurately.

"We chose the periportal region of the liver in particular since it plays a key role in bile transport and is often disrupted in liver diseases when the connection of cells responsible for bile transport is blocked," says Anna Dowbaj. Since June 2025, she has been Professor of Integrated Organoid Systems at the TUM School of Life Sciences; her lab is based at the TUM Center for Organoid Systems and Tissue Engineering in Garching.

Mechanisms that control aging

The liver has an astonishing capacity to regenerate. "That is why we use it as a model to understand why this regenerative capacity declines with age or is impaired in disease," the researcher says. "This allows us to study how the cells that regenerate the liver communicate with the cells that support this regeneration."

This communication between cells - for example through signaling molecules or direct contact - is at the heart of Professor Dowbaj's research. In regeneration, it is not only important which cells are present. What also matters is how they are connected and which signals they exchange.

Regulating renewal

During her time as a postdoctoral researcher at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Dowbaj studied communication between cholangiocytes, the cells of the bile ducts, and neighboring mesenchymal cells. The research team was able to show that the number of contacts between these cells influences whether the cholangiocytes multiply - or whether their growth is stopped.

This is important for liver regeneration. After injury, new cells need to be formed. At the same time, growth must not get out of control, as this can contribute to disease. Cell-to-cell contacts therefore have a regulatory effect on tissue renewal. In subsequent work, Dowbaj contributed to a study that used three-cell liver assembloids to model aspects of biliary fibrosis in vitro.

Dowbaj is now using the same models to better understand aging processes. "We specifically assemble the organoids from cells of different biological ages," she says. "I hope this will allow us to discover mechanisms that control aging."

Keeping the whole body in view

The liver is the body's central metabolic organ. It processes nutrients, breaks down harmful substances, and produces important proteins. If its function declines with age, this can have consequences for the entire organism. "If we were able to improve the health of the aging liver, this could possibly also improve the health of the entire human body in old age," says Dowbaj. Organoid models could allow researchers in the future to better investigate how liver diseases arise, how drugs work, and which approaches might help improve liver function in old age.

In the long term, Dowbaj also wants to apply her findings to other organs, such as the colon and small intestine. This is one reason why she particularly values the interdisciplinary collaboration at the TUM Center for Organoid Systems and Tissue Engineering. "Here, researchers work on organoid models of different organs. This means we can study not only individual tissues, but also communication between organs in the body."