Prerequisite for protective effects of fasting is an increase in the concentration of the endogenous substance spermidine in the organism / international study involving the team of Stephan Sigrist from Freie Universität
According to the results of an international study involving the Freie Universität Berlin, fasting can prolong life and increase the health span. As the researchers, including the team led by neurobiologist Stephan Sigrist, discovered, these effects are due to the upregulation of the body’s own substance spermidine. The team investigated the effects of fasting on fitness, healthspan and lifespan as part of an international study involving 20 universities led by the Karl-Franzens University of Graz. The key finding of this study is that the positive effects of fasting depend on the substance spermidine being upregulated in the body. Spermidine is an endogenous polyamine - a nitrogen compound in human cells whose concentration decreases with increasing age. Earlier studies by the Sigrist group had already shown that dietary spermidine administration can slow down the ageing process in model organisms. The results of the study were published on Thursday in the latest issue of Nature Cell Biology.For several decades, life expectancy has been increasing in most parts of the world, while the health span, the time a person can live in good health, has not increased to the same extent. This means that more and more people in old age are suffering from age-related illnesses, in particular declining cognitive fitness. This represents a considerable psychological, social and socio-economic burden for our societies," emphasizes Stephan Sigrist from the Department of Biology, Chemistry and Pharmacy at Freie Universität. Calorie reduction and intermittent fasting extended the lifespan and health span of model organisms and improved human health. "Fasting could therefore very probably be a preventive and protective measure to reduce age-related diseases." However, fasting is difficult to integrate into everyday life and is hard for many people to keep up. Substances that are able to mimic the positive effects of fasting on the body ("fasting mimetics") are therefore increasingly being investigated. These include the polyamine spermidine. The compound bears the name because it was first found and described in male seminal fluid.
Work led by Stephan Sigrist from the Free University of Berlin has shown in recent years that the substance spermidine has properties that can mimic the positive effects of fasting on the body ("fasting mimetic"). Spermidine levels decrease with age, and dietary spermidine administration has been shown to slow down ageing processes in model organisms. The Sigrist lab was able to show that the administration of spermidine directly activates a molecular process called hypusination, which boosts the activity of mitochondria in the brain - and thus protects cognitive performance in ageing model organisms. However, the extent to which spermidine and hypusination are actually involved in the effects of fasting in humans remains unclear.
Stephan Sigrist’s laboratory participated in a study by an international research network of over 20 universities (led by Sebastian Hofer and Frank Madeo from the Karl-Franzens University of Graz), which investigated the molecular basis and effects of fasting and the possible role of spermidine in a systematic study, including data obtained in humans. Stephan Sigrist’s team investigated the extent to which fasting effects in the fruit fly Drosophila were dependent on spermidine-mediated hypusination. "As expected, fasting processes improved fitness, healthspan and lifespan," states Stephan Sigrist. "The decisive finding of the study is that this fasting-induced increase in vitality was absolutely dependent on an increase in the body’s own spermidine concentration." Pharmacological and genetic interventions in model organisms proved that the positive effects of fasting were switched off when the increase in spermidine was prevented.
The research consortium also found that chronic inflammation, such as arthritis, and heart function in ageing model organisms could be positively influenced by fasting. However, this was only observed when the body’s own upregulation of spermidine was not experimentally impaired. At the molecular level, it was shown that the spermidine-induced molecular process of hypusination is of central importance for the protective effects of fasting. In addition, the triggering of autophagy, a cellular cleansing program that breaks down age-associated cellular debris, is also crucial. According to the researchers, these findings contribute to the scientifically sound development of strategies through which the fundamental effect of fasting can be used to slow down the physical decline associated with ageing. (cwe)
’024 -01468-x
Since its founding in December 1948, the academic ethos of Freie Universität Berlin has been determined by three values: Truth, Justice and Freedom.
