The aging process is often linked to the appearance of cognitive disorders, depressive states or memory loss. Scientists from the Institut Pasteur, CNRS and Inserm have discovered that the administration of the GDF11 protein, already known to regenerate murine nerve cells, improves cognitive abilities and also reduces depressive states in elderly mice. . They also highlighted the mechanism of action of this protein in different mouse models. The scientists then looked further into these results on depression, and showed that in humans, the level of GDF11 is inversely linked to depressive episodes. The results of this study are published in the journal Nature Aging on February 2, 2023.
The aging process is often linked to the appearance of neurological disorders: cognitive decline, memory loss or even mood disorders such as depression. Previous studies have shown that the growth factor “GDF11”, a protein present in the blood, had a beneficial effect on olfactory perceptions and on the process of generation of new cells in the brains of aged mice. The mechanism of action of GDF11 in the brain still remained unknown.
Researchers from the Institut Pasteur, CNRS and Inserm have discovered that long-term administration of the GDF11 protein to elderly mice improves their memory capacities and significantly reduces behavioral disorders related to a depressed state, allowing them to find a behavior similar to younger mice.
The scientists continued their study in different mouse models that are aged or present with behavioral disorders linked to a depressive state, as well as in neuron cultures. in vitro, which allowed them to identify the molecular mechanism of action of GDF11. They have in fact discovered that the administration of GDF11 activates in the brain the natural process of intracellular cleaning, called “autophagy”, and the elimination of senescent cells. The GDF11 protein thus indirectly increases cell renewal in the hippocampus and restores neuronal activity.
In order to better understand the link between depressive disorders and the GDF11 protein in humans, scientists from the Institut Pasteur, CNRS and Inserm, in collaboration with scientists from McMaster University, quantified the protein in the blood serum of an international cohort of young patients with depressive disorders. They observed that GDF11 levels are significantly lower in these patients. Moreover, by measuring the levels of this protein at different stages, the scientists observed a fluctuation in the rate depending on the depressive state.
« This work provides clinical evidence linking low blood levels of GDF11 to mood disorders in patients with depression » says Lida Katsimpardi, researcher in the Perception and Memory Unit at the Institut Pasteur, affiliated with Inserm within the Institut Necker Enfants Malades and co-last author of the study. « In the future, this molecule might be used to diagnose, like a biomarker, depressive episodes. It might also serve as a therapeutic molecule for the treatment of cognitive and affective dysfunctions. she concludes.
Press release, Inserm, February 21, 2023
