22 April 2020

Stress sensor in cells delays ageing


The ageing process of cells is an interaction between cell stress and stress response. This is supported by new research results from the University of Copenhagen. The researchers have shown how an already known stress sensor works, and that an organism ages faster if the sensor is turned off.

Caenorhabditis elegans
The microscopic worm Caenorhabditis elegans

Stress is a two-sided state that may have both positive and negative consequences. Short-term stress can put you on the alert and make you perform better. Prolonged stress can damage your health. This applies to individuals as a whole, but it also applies all the way down to the cellular level. Therefore, to understand ageing, it is important to understand how cell stress functions.

Researchers from the Center for Healthy Aging at the Faculty of Health and Medical Sciences, the University of Copenhagen, have for several years hypothesised that an interaction between cell stress and the cells' own response to it plays a role in the ageing process: Stress speeds up the ageing, while the cells’ stress response delays it.

By exposing microscopic worms to stress in the laboratory, the researchers have now shown how a particular sensor detects cell stress and alerts the organism that something is not working properly. Without that specific sensor, the worms will age faster.

‘We have studied a particular type of cell stress that damages the ribosomes. The ribosomes produce all the proteins of the cell, so if they do not work, the cell cannot function either. When a cell detects that it has a problem producing proteins, it starts a stress response. Until now, we have not known how this response was working or whether it was important for the organism as a whole, because it has only been studied in cell cultures and not on whole organisms’, says Professor Simon Bekker-Jensen from the Center for Healthy Aging.

Turned-off sensor means faster ageing

In the laboratory, the researchers have been testing two different versions of the microscopic worm, Caenorhabditis elegans. One where the ZAKa sensor was naturally present, and one where the same sensor had been turned off. By exposing the worms to stress in the form of increased temperatures, they were able to study the differences in the worms’ stress response. The worms in which the sensor had been turned off lived shorter.

‘We can thus conclude that this sensor plays an important role in the ageing process for a whole organism. In our study, we can also see that the sensor does not have a phenotype. There is no difference between the worms with and without a sensor – until we expose them to stress in the form of a temperature increase. We do not yet know which natural stress factors the sensor is designed to respond to’, says PhD student and first author of the study, Anna Constance Vind.

The finding is one of many pieces in the puzzle when trying to understand the very basic biology. And while it may seem that microscopic worms and humans do not have much in common, many of the basic building blocks are the same. Therefore, we can gain valuable knowledge about human ageing by studying cell stress in worms.

The evolutionary function

The studied sensor has been known for many years. This is partly because it is precisely this sensor that is activated when the cells are attacked by ricin. Ricin is a toxic protein produced from castor beans from the Palm of Christ, and it has been used in terror attempts and attacks. However, because the cells are not naturally exposed to ricin in their lifetime, the evolutionary function of the sensor is probably different.

‘We would like to find out when and why this sensor becomes naturally activated during the lifetime of an organism. Both ricin poisoning and our laboratory-generated stress are artificial influences and thus, they cannot be the reason why the cells have this sensor’, says Simon Bekker-Jensen.

Therefore, the next step for the researchers is twofold. One goal is to find out when the sensor is naturally activated. The second goal is to investigate whether the sensor has the same function and importance in larger organisms. For now, the researchers are in the process of making the same tests on mice – an organism that is somewhat closer to humans than the microscopic worms.

The study ‘ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains‘ has been published in the journal Molecular Cell and is financed by Lundbeckfonden 

Professor Simon Bekker-Jensen
+45 20 20 49 93

Press Officer Amanda Nybroe Rohde
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