Alter, was machst du?*
By University Hospital Bonn
The key to this discovery lies in the protein switch mTOR,
which influences cognitive performance and metabolic processes throughout the
body. These findings have been published in the journal ACS
Pharmacology & Translational 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 aging 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 aging 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 aging brain by reducing the formation of new synapses on a nerve cell and thus also cognitive abilities.
“Therefore, anti-aging strategies based on the reduction of
mTOR activity might not only be ineffective but even counterproductive against
brain aging. 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 aging process in the brain
In a previous study, 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-aging 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 has 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.”
Reference: “Bidirectional Effect of Long-Term
Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome” by Andras
Bilkei-Gorzo, Britta Schurmann, Marion Schneider, Michael Kraemer, Prakash
Nidadavolu, Eva C. Beins, Christa E. Müller, Mona Dvir-Ginzberg and Andreas
Zimmer, 14 August 2024, ACS Pharmacology & Translational Science.
DOI:
10.1021/acsptsci.4c00002
This work was funded by the German Research Foundation and
the German Excellence Strategy.
*What is dude in German slang?
Meaning: “Dude” or “Man.”
