Project description
Restoring hypothalamic health to combat metabolic ageing
As global life expectancy rises, societies face a growing burden of obesity, which worsens the metabolic decline naturally associated with ageing. The hypothalamus, the brain’s metabolic control centre, is particularly vulnerable to these changes, specifically in neurons that express the protein Tbx3. Supported by the Marie Skłodowska-Curie Actions programme, the OBrAgeing project will investigate whether unhealthy diets accelerate brain ageing through Tbx3-dependent mechanisms. By using advanced mouse models and single-cell profiling, the project will examine how dietary cues and age impact these specific neurons. Furthermore, the project aims to determine if restoring Tbx3 levels can reverse metabolic dysfunction. Ultimately, OBrAgeing’s goal is to uncover how brain health influences whole-body ageing, offering potential strategies to maintain metabolic health across the lifespan.
Objective
As global life expectancy rises, societies are concurrently facing a growing burden of obesity, a condition known to exacerbate the metabolic decline naturally associated with ageing. While ageing disrupts metabolic function across multiple organs, the role of specific brain neurons in this decline remains poorly defined, despite the brain's central role in coordinating whole-body energy homeostasis. The hypothalamus is a critical brain region for regulating systemic metabolism and is particularly vulnerable to age-related molecular and cellular alterations, notably within neurons expressing the transcription factor T-box 3 (Tbx3). Dr. Quarta’s research has identified Tbx3 as a critical determinant of neuronal identity through life, with its loss leading to metabolic dysfunction and obesity. Both ageing and chronic exposure to obesogenic diets diminish hypothalamic Tbx3 expression.
Tbx3 also modulates cellular senescence, a key hallmark of neuronal ageing. Therefore, I hypothesize that obesogenic diets may accelerate hypothalamic neuronal ageing through Tbx3-dependent mechanisms, thereby contributing to systemic metabolic decline in ageing individuals. To test this, we will employ reporter mouse models to profile Tbx3-expressing hypothalamic neurons under ageing in both control and obesogenic diets at single cell resolution (single cell transcriptomics and electrophysiology assessments). We will examine how dietary and age-related cues modulate Tbx3 expression and induce molecular features of neuronal ageing. Finally, using in vivo viral-mediated gain- and loss-of-function approaches, we will assess whether modulating Tbx3 levels can restore neuronal integrity and systemic metabolic control in aged mice exposed to control or obesogenic diets. This project seeks to unravel the neurobiological underpinnings of neuronal and whole-body metabolic ageing in response to dietary cues, with potential implications for maintaining metabolic health across the lifespan.
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 health sciences nutrition
- medical and health sciences basic medicine physiology homeostasis
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
Funding Scheme
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2025-PF
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75654 Paris
France
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