Iodine, zinc, iron, copper, selenium, and manganese are essential trace elements our body needs in tiny quantities. Yet basic knowledge about these micro nutrients is still scarce. In the DFG-funded research unit “TraceAge”, researchers study complex interactions between trace elements as well as their role in the aging process and in diseases in older age.
Lab worms live in the dark, but they don’t mind. In their culture dishes in the incubator they have all they need: abundant bacteria to feed on, a pleasant temperature of 20 degrees centigrade, and many others of their own kind. The transparent nematode Caenorhabditis elegans is but 1 millimeter long. Originally a soil organism, it has been a common sight on agar plates in scientific laboratories all over the world since the 1960s.
Here, at the Institute of Human Nutrition, the worm is also well-known and used as a model organism. “It is very well-researched and easy to modify genetically,” PhD student Jessica Baesler explains. Besides, nematodes are easy to keep, multiply rapidly, and are easy to examine. These properties make them a good choice for Baesler, too, who wants to find out how a specific diet affects the nematodes’ development.
The tests carried out by Baesler are part of the extensive study “TraceAge”, in which 6 teams of 36 researchers from a variety of disciplines such as epidemiology, clinical medicine, toxicology, analytical chemistry, food chemistry, and nutritional physiology study the effects of certain substances in food on the health of elderly people. Their focus is on trace elements which the body needs only in very small quantities.
In “TraceAge”, the researchers are looking at 6 of these micronutrients – selenium, iodine, copper, zinc, iron, and manganese – that are involved in the regulation of the immune system, the production of proteins, and the activation of hormones, for instance. “In order to be able to survive, humans have to take up trace elements,” underlines Professor Tanja Schwerdtle who directs the study. But our knowledge of this is only a few decades old. Hence, research on the effects of micronutrients on health or aging is still in its infancy. “As yet, we know very little,” Schwerdtle summarizes. But in general, the German population is comparatively well-supplied with trace elements, and acute deficiencies are rare. Some people – especially women – show mild symptoms of an iron-deficiency anemia. The researchers suspect an undersupply of selenium as well, since the soil in Germany is poor in selenium resulting in a low concentration of selenium in crops. “As for selenium, we don’t know exactly what amount is really needed,” Schwerdtle explains. An under- or oversupply might increase the risk of cardiovascular diseases, cancer, and diabetes. “It is a very sensitive issue, and only a few markers are known to indicate whether someone is sufficiently supplied,” she says.
The same applies to the other trace elements studied by “TraceAge”. Above all, the researchers are interested in the interactions between micronutrients. “It doesn’t make sense to look at them separately, since they interact,” Schwerdtle explains. The researchers also want to develop more accurate ways of measuring trace elements and their effects. From the full picture of all parameters, a fingerprint of a person’s health status will be created. For this purpose, so-called function markers have to be developed. These could be metabolic products, molecules, certain proteins, or hormones that can be found in blood serum and indicate how well the body is supplied with certain micronutrients. At the same time, these markers should allow for predictions of potential diseases resulting from under- or oversupply.
For the same purpose, Baesler puts nematodes under the microscope. They were put on a special diet to under- or oversupply them with one or several trace elements, and now their development is inspected: Do they produce more or fewer eggs? Do they wiggle across the substrate as usual, or do they move differently? Do they show organ deformities or abnormalities? Baesler uses these parameters to understand whether the respective diet has been beneficial or detrimental to the worms.
The way the nematodes move may also indicate whether their nervous system has been damaged. This aspect is particularly important in the research, as trace elements seem to be associated with neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s. The genome of some of the nematodes has been altered to make them more vulnerable to neuronal damage. If Baesler finds indications of, let’s say, her “Alzheimer’s nematodes” displaying more damage on certain diets, she may examine them once again at the molecular level using marked nerve cells of nematodes. In addition, she analyzes which genes are active, which proteins are formed, and in which cells and organs trace elements accumulate. Her results will provide insights into whether and how trace elements are associated with neurodegenerative disorders in humans, too.
The nematode model of the “TraceAge” researchers is just one of many levels at which the various questions are studied. The researchers also use cell cultures, mice, and the comprehensive data of the EPIC Potsdam study to get a holistic picture of how trace elements function. The wealth of data compiled in the EPIC long-term study – through which blood samples and data of thousands of test persons have been collected since the 1990s – has already produced some exciting results.
Analyses of the serum of test subjects who had blood samples taken every 20 years confirm a hypothesis nutritional researchers have had for some time: With age, copper concentrations in serum increase, while zinc concentrations drop. Dietary changes in older age could have provided an explanation for this phenomenon. However, the “TraceAge” researchers were able to demonstrate in an experiment with mice that the zinc and copper concentrations in older mice changed even though they were on the same diet as younger mice. Tanja Schwerdtle suspects that, among other things, “physiological processes in the intestine change with age, making zinc absorption more difficult”. This has consequences not only for the immune system, but also for aging processes, as many zinc-activated enzymes are involved in the repair of DNA damage.
While the researchers are still in the midst of their work, they are already planning the next major studies as the research area of trace elements is largely unexplored. Aside from neurodegenerative disorders, the spotlight will be on bone health. The analysis of measurements needs to be optimized and refined, and imaging techniques will be used to determine the brain regions or organs where trace elements accumulate. In addition to that, other age groups and the effects of micronutrients during pregnancy will be studied. Besides, the interactions between trace elements and vitamins have largely not been researched, either.
So there is still a lot of work to do for researchers and nematodes alike. The nematodes will probably take it easy: If food runs out in their incubator, they will turn stiff and survive hunger periods of up to three months as long-time larvae. Once food becomes available again, they will wake up and continue to grow.
“TraceAge – Interactions of essential trace elements in healthy and diseased elderly” is an interdisciplinary research unit funded by the German Research Foundation (DFG). Spanning multiple disciplines, it investigates interactions of essential trace elements and their role in diseases and develops new measuring methods.
Participants: University of Potsdam, German Institute of Human Nutrition Potsdam Rehbrücke, Friedrich Schiller University Jena, Charité – Universitätsmedizin Berlin, Technical University Berlin
Prof. Dr Tanja Schwerdtle studied chemistry and food chemistry at the University of Karlsruhe. She has been Professor of Food Chemistry at the University of Potsdam since 2013.
This text was published in the university magazine Portal Wissen - Two 2019 „Data“.