Modeling metabolism in the aging brain

Lead article

Figure showing metabolic adaptability networks in young and aged brains.

Breakdown and repair of metabolism in the aging brain

Polina Shichkova
Jay S. Coggan
Lida Kanari
Elvis Boci
Cyrille Favreau
Stefano Maximiliano Antonel
Daniel Keller
Henry Markram

Frontiers in Science

doi 10.3389/fsci.2025.1441297

62,953 views
4 citations

Expert insights

3D model generated by the researchers representing the breakdown and repair of metabolism in the aging brain that might lead to dementia. Using an illustration of a dense, colorful neuronal network, it shows tangled red, yellow, and blue lines that represent neurons, glia, and vasculature.

ARTICLE EVENT

Discussion with the article authors

Join a complimentary virtual symposium on next steps for modeling metabolism in the aging brain.

Date & time: 7 May 2025 at 16:00 CEST

Frontiers in Science Editorial

Published on 25 Mar 2025

Pathways toward and away from a metabolic cliff during brain aging

Loss of metabolic flexibility may explain age-related susceptibility to neurodegenerative diseases, necessitating interventions that support brain energy resilience and delay cognitive decline, contends Prof Mark P. Mattson, Johns Hopkins University School of Medicine, USA.

Portrait of Prof Richard B. Buxton against a plain backdrop. He is looking at the camera and smiling.

Frontiers in Science Viewpoint

Published on 25 Mar 2025

Recharging the brain’s batteries: a thermodynamic perspective on modeling brain energetics

Applying a thermodynamic perspective to models of brain energy metabolism could more fully capture cellular energy balance and its role in brain aging, argues Prof Richard B. Buxton, University of California San Diego, USA.

Portrait of Luc Pellerin against a green backdrop. He is looking at the camera.

Frontiers in Science Viewpoint

Published on 25 Mar 2025

The future of healthy brain aging will be metabolic: a predictive lesson from data-driven modeling

Astrocyte-neuron metabolic interactions are crucial targets for mitigating neurodegenerative risk, and computational modeling can help us develop interventions to preserve or restore brain health, asserts Prof Luc Pellerin, Université de Poitiers, France.

Portrait of Prof Renaud B. Jolivet in front of a building and trees. He is smiling at the camera.

POLICY OUTLOOK

Published on 25 Mar 2025

Simulating aging to increase human healthspan: how in silico life sciences could tackle real societal challenges

Extending the human healthspan and easing the societal burden of aging-related diseases require long-term funding for infrastructures that support large-scale data collection and systems-based aging research, advocate Prof Renaud Jolivet and colleagues, Maastricht University, Netherlands.

Key points

This is the most comprehensive molecular model of the neuro-glia-vascular system to date, integrating the key cellular and subcellular systems, molecules, metabolic pathways, and processes required to couple neuronal electrical behavior with brain energy metabolism and blood flow.

Supplied with publicly available RNA sequencing data, the model closely reproduces known aging-related changes in brain metabolism and electrical activity, validating its utility as a research tool.

The model predicted reduced robustness, flexibility, and metabolic adaptability in the aged brain and identified various aging-associated transcription factors and potential anti-aging therapies and strategies.

We show that astrocytes may subserve the metabolic stability of neurons during aging, calling into question previous assumptions about selfish glia.

This open-source resource should help accelerate research to improve our understanding of age-related neurodegenerative diseases (such as dementia) and how their onset could be prevented or delayed.

For all readers

Infographic on brain metabolism simulation predicting aging strategies, integrating neuro-glia-vascular factors and suggesting interventions for aging brains and dementia.

EXPLAINER

Published on 25 Mar 2025

Changes in metabolism impair neurons in aging brains

A summary of the lead article in a Q&A format, with infographics and a video.

Illustration of researchers exploring how factors like diet, exercise, or medicines might keep our brains healthier and avoid dementia for longer.

Frontiers for Young Minds

Published on 25 Mar 2025

Can We Keep the Brain Energized as it Ages?

A version of the lead article written for—and peer reviewed by—kids aged 8-15 years.

News

PRESS RELEASE

Published on 25 Mar 2025

Most in-depth simulation of brain metabolism yet reveals new targets for future dementia treatments

A new model of brain metabolism—the most complex ever generated—shows how altering key chemicals could restore aged cells to their youthful activity and resilience.

NEWS STORY

Published on 25 Mar 2025

Computer model of age-related changes in brain metabolism could point to rejuvenating strategies

A new open-source model of brain metabolism, developed by scientists at École Polytechnique Fédérale de Lausanne (EPFL), has shown how altering key chemicals could restore aged cells to their youthful activity and resilience.