A team of researchers from Berlin, Dortmund, and Graz are investigating how the substance spermidine can protect aging brain cells.

According to a recent study, age-related memory loss may be preventable. Researchers from Freie Universität Berlin, the NeuroCure Cluster of Excellence, the Leibniz-Institut für Analytische Wissenschaften (ISAS) in Dortmund, and the University of Graz found that the substance spermidine – something that is present in all human cells – can protect the mitochondria found in aging brain cells. Mitochondria are known as the “powerhouses of the cell” and contain their own genetic material. The use of spermidine enables them to remain functional, as the research team was able to show through investigating the effect of spermidine on the brains of aging fruit flies. The study showed that an uptake of spermidine increased mitochondrial activity in the flies, reducing age-related memory impairment. The study appears in the current edition of the journal Cell Reports.

The team was able to show that an uptake of spermidine can significantly increase mitochondrial activity in aging flies, and the researchers were able to identify a mechanism known as “hypusination” as the central factor in this outcome. In hypusination, part of the spermidine molecule is transferred to a specific factor that represents a kind of motor within protein synthesis. “The hypusination reaction seems to be the cause of the improvement in mitochondrial function after a spermidine boost,” explains Professor Stephan Sigrist, ECN Member. “Hypusination can be observed in all animals, including humans. It is directly regulated by spermidine and may explain much of the effect this substance seems to have.” The lead author of the study, Yong-Tian Liang, notes, “Spermidine-induced hypusination could prove to be an important diagnostic and therapeutic indicator for brain aging brought about by the loss of mitochondrial function.”

Professor Sigrist’s team worked alongside teams led by Albert Sickmann (ISAS Dortmund) and Frank Madeo (University of Graz) respectively. Together, the researchers will now explore their hypothesis in aging mice and, eventually, in aging humans. At this final stage, they will work together with the Cluster of Excellence NeuroCure, which already supports Professor Sigrist’s work. NeuroCure is a Cluster of Excellence in the neurosciences with researchers based within Charité – Universitätsmedizin Berlin, a single medical faculty serving both Freie Universität und Humboldt-Universität zu Berlin.

Age-related memory loss frequently accompanies the aging process in humans. Because human life expectancy in general is constantly rising, this kind of memory impairment is becoming more prevalent. As such, it has an immense impact on society as a whole as well as on individuals, and also has considerable financial implications. Most people want to retain a healthy mind and body right up into old age, but this desire is often, if not always, frustrated by the effects of physical impairment and illness.

“Our health and the ability of our cells to function are based on complex mechanisms,” says Sigrist. “As with any other complex mechanism, sometimes things can go wrong. Protein cells can decay and clump together. But even the tiniest powerhouses within our cells, the mitochondria, can develop toxic substances such as oxygen radicals, which go on to damage the cells themselves.” Sigrist explains that this kind of process accelerates the aging of the most complex organ in the human body – the brain. This can impair memory functions in different ways, including various kinds of neurodegeneration such as Alzheimer’s disease. Scientists are therefore keen to identify substances and agents that can help prevent or at least slow down these aging processes. Researchers at the University of Graz previously found that spermidine is one of the most promising substances in this context, and it is currently being tested in humans.

Although it was first discovered in sperm, spermidine is actually found in nearly all cells in the human body. But the concentration of spermidine in humans decreases with age. In animal models using fruit flies or mice, the addition of spermidine as a food supplement resulted in a prolonging of the healthy life span. It also slowed down age-related memory loss. But we don’t yet know enough about the mechanisms underlying the effect of spermidine in the brain – knowledge that is needed in order to continue optimizing therapeutic approaches. This is what the study carried out by the research team aims to find out.

Source: FU Press relaese

Original publication:

Liang et al., eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction. Cell Reports, 13.4.2021, DOI: 10.1016/j.celrep.2021.108941.

Contact:
Prof. Stephan J. Sigrist
ECN Member
Department of Biology
Chemistry, Pharmacy
Freie Universität Berlin,
Email:stephan.sigrist(at)fu-berlin.de