Project description
Astrocyte metabolism and cognitive ageing
Nearly 40 % of dementia cases are affected by modifiable factors such as nutrition and physical activity. Although this suggests that diet and lifestyle are important for brain health, the biological mechanisms connecting lifestyle to cognition remain unclear. Astrocytes, situated between blood vessels and synapses, could be the cells responsible for translating lifestyle changes into brain function. The ERC-funded NeuroSTARS project will investigate how astrocytic metabolism adapts to diet and exercise by producing metabolites that can regulate gene expression through epigenetic mechanisms. In this context, researchers will utilise mouse models and advanced metabolic and cognitive tools to uncover lifestyle-driven astrocytic pathways that shape cognition. Collectively, the work will offer new strategies for preventing age-related cognitive decline.
Objective
Cognitive impairment is a major source of disability and dependence during aging. Up to 40% of dementia cases are attributable to modifiable environmental risk factors, namely lifestyle, which can be actionable for prevention before the onset of cognitive decline. Physical activity and nutrition comprise promising modifiable factors affecting cognitive aging, but how the lifestyle affects cognition is not fully explained. Because of their unique location at the interface between blood vessels and synapses, astrocytes are strategically positioned to translate lifestyle contexts into specific cognitive shapes. Work from our group has demonstrated that astrocytic metabolism is remarkably dynamic and alternates lactate, ß-hydroxybutyrate and acetyl-coenzyme A production. Importantly, preliminary data indicate that these metabolites directly bind histones within astrocytes as epigenetic regulatory adaptive mechanisms. In NeuroSTARS, we will address whether such epigenetic adaptation is dictated by lifestyle-driven modulation of astrocytic metabolism to underpin cognitive performance across the lifespan. In mice subjected to controlled physical activity and dietary contexts, in combination with genetic manipulation of pivotal metabolic pathways in astrocytes, using cutting-edge metabolism and cognition assessment tools, we will (i) identify how astrocytic metabolism adapts to different lifestyle contexts throughout life, (ii) decipher the lifestyle-induced metabolic pathways that impact on metabolites-driven epigenetic regulation in astrocytes, and (iii) define the mechanism that causally links lifestyle-induced metabolism-driven epigenetic regulation within astrocytes with cognition across the lifespan. The expected output will reveal that the metabolism of astrocytes is instrumental in the coupling between lifestyle and age-associated cognitive decline, challenging the view that it merely serves to meet the energy needs of neurotransmission.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia
- medical and health sciences health sciences nutrition
- natural sciences biological sciences genetics epigenetics
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-ADG
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37008 Salamanca
Spain
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