New brain metabolism model reveals key targets for reversing aging

The most extensive model of the brain metabolism, with more than 16,800 biochemical interactions, has identified important goals to reverse the age -related decrease in brain function. The new analysis of complex interactions between neuronal activity, metabolism and blood flow showed that the recovery from blood chemistry to juvenile levels through food, exercise and supplements could improve the resilience of the brain against damage. Scientists can now use this model to find ways to prevent age -related diseases, such as dementia.

A new open-source model of brain metabolism-the most complex ever-generated-has shown how changing important chemicals could restore outdated cells to their youthful activity and resilience.

The researchers who write in science in limits discovered that reducing blood glucose, as well as increasing blood keton and lactate levels, could help repair the metabolic function in aging brains. These can all be achieved potentially by changes in lifestyle, including exercise and the food we eat.

The findings come to date from the most extensive computer model of brain metabolism, which contains more than 16,800 biochemical interactions between proteins and chemicals about brain cells, supporting cells and blood.

Scientists can now use this open-source model to find ways to prevent age-related diseases, such as dementia.

This study offers X -ray view in the battery that drives the brain. We can now follow how the brain energy system ages at the molecular level. “

Henry Markram, professor of neuroscience at École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, senior author of the study

Juvenile resilience

The detailed simulation – an analysis of complex interactions between neuronal activity, metabolism and blood flow – is based on data from human and rodent brain. It gives a glimpse into how brain metabolism breaks down with age and impedes its function, and identifying usable potential ways to restore youthful resilience. We place heavy demands on the neurons of our brains to navigate our daily lives. This requires a lot of energy and support, which comes from blood supply and supporting ‘glial’ cells called astrocytes.

To understand the impact of aging on the brain’s metabolism, the team recorded these elements in their model, which they used to compare the metabolic states of young and old brains. In total, they calculated the impact of age -related changes on 16,800 interactions between proteins and chemicals over neurons, Glia and the blood. The model revealed that changes in the quantities of certain molecules can have complex knock-on effects, which can influence many different metabolic reactions at the same time. This meant that the cells were more vulnerable to damage because they were less able to adapt and restore themselves.

It also emphasized potential drug goals, as well as the potential advantage of supplementing with nicotinamide adenined and nad) – a molecule that plays a crucial role in the energy supply of the brain. NAD boosting supplements were previously studied as a potential healthy aging therapy.

Dr. Polina Shichkova, the main author of the Frontiers in science Study, said: “We were surprised by the mutual dependencies of molecular reactions, tight regulation and signaling within this system. We showed how the vulnerability of brain metabolism is the result of the collapse of many metabolic routes, not just one, a finding that calls multiple target therapies.”

A discovery that goes beyond lifestyle factors

The discovery enabled the team to understand the complex molecular mechanisms that determine the robustness, flexibility and adaptability of the aging brain. By changing the quantities of important chemicals, the researchers felt that the old cells could be restored to their youthful activity and resilience.

“Our findings go beyond what we already knew about these lifestyle factors,” said Shichkova. “Our model offers a detailed molecular mechanism of these practices that will help researchers develop more precise or effective interventions.”

The researchers also used the model to identify possible goals of the drug that can restore resilience against brain cells. They identified a protein called estrogen -related receptor Alpha (ESRRA), which is connected to the predicted age -related decrease. This finding can lead to further research into the development of effective treatments to support aging neurons.

“Although there are usually many steps between the predictions of a computer model and practical guidelines for people, some suggestions of our model already include approved supplements, nutritional changes or lifestyle habits,” Shichkova said.

A tool for further research

The researchers built the model with the help of publicly available data on the gene activity of brain cells in people and mice. When they compared its results with experimental data that were not used for training, the model accurately predicted changes in biochemical activity in neurons with age. This has verified its usefulness as a research tool and the value of his findings.

Shichkova said: “This modeling approach was needed because of the complexity of the system, which cannot easily be studied experimental. Although the model is built from experimental data, the predictions of the simulation of the behavior of the molecular network will in turn lead further biological research.”

The study was part of the Blue Brain project, which was aimed at developing simulations and reconstructions of the mouse brain. The model will be available on the Open Brain platform organized by the Open Brain Institute, allowing neuroscientists to perform simulations based on the research.

The team hopes that this research will help speed up age -related neurodegenerative diseases, such as dementia. Energy metabolism is a potential cause of such circumstances, so further research on this, as well as validating the findings in human test subjects, can help find new ways to stimulate the defense of the brain.
This study was supported by financing at the Blue Brain Project, a research center of the École Polytechnique Fédérale de Lausanne, from the Eidgenössische Technische Hochschule (ETH) Board of the Swiss Government of the Swiss Federal Institutes of Technology.