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Bonn researchers clarify the influence of treatment with tetrahydrocannabinol on the metabolic switch mTOR: A low-dose long-term administration of cannabis can not only reverse aging processes in the brain, but also has an anti-aging effect. Researchers from the University Hospital Bonn (UKB) and the University of Bonn together with a team from Hebrew University (Israel) have now been able to show this in mice. They found the key to this in the protein switch mTOR, whose signal strength has an influence on cognitive performance and metabolic processes in the entire organism. The results are now presented in the journal "ACS Pharmacology & Translation Science".
Information about the availability or scarcity of resources is of crucial importance for the regulation of metabolism. The so-called metabolome is a complex reaction network that summarizes all metabolic properties of a cell or tissue. In higher organisms, the protein mTOR [Mechanistic Target of Rapamycin] is the central hub for cell growth and metabolism. As a sensitive intracellular energy sensor system, its activity has a major influence on ageing by regulating cell metabolism. A reduction in mTOR activity through a low-calorie diet, intensive physical activity or pharmacological treatment therefore has a general anti-ageing effect. In addition to an altered metabolism, the ageing of the brain is also accompanied by a reduced ability to change neuronal connections, known as synaptic plasticity. Reduced mTOR activity can therefore also have a negative effect on the ageing brain by reducing the formation of new synapses on a nerve cell and thus also cognitive abilities. "Therefore, anti-ageing strategies based on the reduction of mTOR activity might not only be ineffective but even counterproductive against brain ageing. In our current work, we have now found a strategy to solve this dilemma," says Prof. Dr. Andreas Zimmer, Director of the Institute of Molecular Psychiatry at the UKB and member of the Cluster of Excellence ImmunoSensation2 at the University of Bonn.
Cannabis reverses the ageing process in the brain
In a previous study [https://www.nature.com/articles/nm.4311], the Bonn researchers, together with a team from the Hebrew University of Jerusalem, were able to show that long-term, low-dose administration of tetrahydrocannabinol (THC), the active ingredient in cannabis, has an anti-ageing effect on the brain by restoring cognitive abilities and synapse density in old mice. Whether changes in mTOR signaling and the metabolome are linked to the positive effects on the aging brain had remained an open question. "We have now been able to show that treatment with THC has a tissue-dependent and dual effect on mTOR signaling and the metabolome," says Dr. Andras Bilkei-Gorzo from the Institute of Molecular Psychiatry at the UKB, who is also a researcher at the University of Bonn. Thus, THC treatment in the brain led to a transient increase in mTOR activity and levels of intermediates involved in energy production and amino acids. The latter enabled an increased synthesis of synaptic proteins and thus the formation of new synapses.
Unexpectedly, on the other hand, the Bonn researchers found a similarly strong reduction in mTOR activity of mice in adipose tissue and in the content of amino acids and carbohydrate metabolites in blood plasma as after a low-calorie diet or after intensive physical activity. "We concluded that long-term THC treatment initially has a cognition-enhancing effect by increasing energy and synaptic protein production in the brain, followed by an anti-aging effect by decreasing mTOR activity and metabolic processes in the periphery," says Bilkei-Gorzo. "Our study suggests that a dual effect on mTOR activity and the metabolome could be the basis for an effective anti-aging and cognition-enhancing drug."
Promotion:
This work was funded by the German Research Foundation and the German Excellence Strategy.
Publication: Andras Bilkei-Gorzo et al: Bidirectional effect of long-term Δ9 -tetrahydrocannabinol-treatment on mTOR activity and metabolome; ACS Pharmacology & Translational Science; DOI: 10.1021/acsptsci.4c00002
Link zur Publikation: https://pubs.acs.org/doi/10.1021/acsptsci.4c00002
Press contact:
Dr. Inka Väth
Deputy Press Officer at the University Hospital Bonn (UKB)
Communications and Media Office at Bonn University Hospital
Phone: (+49) 228 287-10596
E-mail: inka.vaeth@ukbonn.de
About Bonn University Hospital: The UKB treats around 500,000 patients per year, employs around 9,500 staff and has total assets of 1.8 billion euros. In addition to the 3,500 medical and dental students, 550 people are trained in numerous healthcare professions each year. The UKB is ranked first among university hospitals (UK) in NRW in the Focus Clinic List, had over 100 million third-party funds in research in 2023 and has the second highest case mix index (case severity) in Germany. The F.A.Z. Institute awarded the UKB first place among university hospitals in the category “Germany's training champions 2024”.
Dr. Andras Bilkei-Gorzo
Institute of Molecular Psychiatry
University Hospital Bonn
Phone: +49+228-6885-317
E-mail: abilkei@uni-bonn.de
Andras Bilkei-Gorzo et al: Bidirectional effect of long-term Δ9 -tetrahydrocannabinol-treatment on mTOR activity and metabolome; ACS Pharmacology & Translational Science; DOI: 10.1021/acsptsci.4c00002
https://pubs.acs.org/doi/10.1021/acsptsci.4c00002 Publication:
Anti-ageing and increased mental capacity through cannabis: Dr. Andras Bilkei-Gorzo clarifies the in ...
Rolf Müller
University Hospital Bonn
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