In fact, almost every cell in the human body can regenerate. However, the nerve cells in the brain are an exception. Researchers can now explain how they can still live to be almost 100 years old.
Brain cells have evolved an elaborate and complex system of adaptations to evade stress and cell death. This is what researchers led by Ruven Wilkens from the Hector Institute for Translational Brain Research at the Central Institute for Mental Health in Mannheim found out.
In aging cells, faulty proteins and damage to the DNA can occur. If this damage gets out of hand because cellular repair programs can do nothing or too little, then this leads to the activation of a cellular suicide program, also known as apoptosis. This is primarily intended to protect against the degeneration of other cells, i.e. the formation of tumors. This programmed cell death is tightly controlled by multiple molecular signaling pathways. It’s different with neurons, because the vast majority of nerve cells are created before birth – and must therefore last as long as possible.
“When cells are stressed or damaged, they usually try to adapt to these conditions, for example by activating reactive repair programs,” explains Prof. Philipp Koch, head of the Hector Institute for Translational Brain Research in a statement. So it seems that this “suicide program” does not exist in the neurons in the brain, or only in a very weak form. To find out how the brain cells still manage to deal with stress and DNA damage and eventually grow older than any other cell in the body, the research team examined the cells at different stages in the laboratory.
To do this, the researchers used human stem cells and converted them into human nerve cells. They allowed these to mature and later compared them to young nerve cells. In addition, the scientists analyzed the gene activity of the older and young brain cells and subjected the cells to various stress tests, such as depriving them of oxygen and exposing them to various toxins. The research team also wanted to determine how the different ancient cells deal with DNA damage.
The researchers saw an almost completely downregulated apoptosis in the mature brain cells. Important genes for the apoptosis signaling pathway are still present, but are not activated in the mature nerve cells. This in turn means that important proteins that initiate cellular suicide are no longer produced. The apoptosis messengers, which are also known as caspases among experts, were produced in the immature nerve cells, but hardly played any role in the mature neurons. “We found that the threshold for entering cell death in human nerve cells is particularly high,” explains Koch.
The researchers saw that human neurons, once mature, are equipped with complex and numerous preventive strategies to protect themselves from stress and cell death. In this way, all mechanisms that lead to cellular suicide are downregulated, while the formation of proteins that have an anti-apoptotic effect are increased.
“It appears that the brain has evolved a very sophisticated, complex and complementary network to protect against cell death, likely an evolutionary adaptation to its reduced regenerative capacity. These protective mechanisms in mature neurons may also partially explain why most neurodegenerative diseases mostly last for many decades can be defended against and only appear at an advanced age. The manifestation of neurodegenerative diseases could be the result of years of accumulated cell stress and damage in combination with a weakening of protective mechanisms,” concludes Koch. The study results were published in the journal “Cell Death
