Periodic Reporting for period 1 - ETERNITY (FuEl ThE bRaiN In healtThY aging and agE-relateD diseases)
Okres sprawozdawczy: 2023-02-01 do 2025-01-31
The global population is ageing, placing increasing pressure on healthcare systems to manage age-related diseases. In Europe, there is a critical need for innovation, expertise, and knowledge to drive advancements in preventing and treating metabolic alterations in the ageing brain. Ensuring brain health throughout life and ageing remains a major priority.
The FuEl ThE bRaiN In healtThY aging and age-related diseases (ETERNITY) project is actively addressing this challenge. With an ambitious goal of understanding how brain metabolic pathways respond to physiological and pathological stimuli, ETERNITY is working to identify new metabolic targets as a foundation for future personalized therapies. Tackling these complex issues requires strong collaboration between academia and industry, and ETERNITY is fostering precisely this environment.
Through its interdisciplinary and intersectoral approach, the project is already generating valuable insights into the mechanisms underlying impaired brain metabolism. By leveraging the complementary expertise of its partners, ETERNITY will also identify novel pharmaceutical targets and developing potential nutritional interventions. Beyond research, the project is strengthening European innovation capacity by training a new generation of researchers who are gaining firsthand experience in academia, the pharmaceutical sector, and the food supplement industry.
Doctoral Candidates (DCs) within ETERNITY are being equipped with cutting-edge methodological skills, innovation-driven thinking, and transferable competencies essential for impactful careers in both research and industry. As the project progresses, its collaborative efforts and training initiatives will contribute to one of the greatest societal challenges of our time: promoting brain health during ageing and delaying the onset of neurodegenerative diseases.
The FuEl ThE bRaiN In healtThY aging and age-related diseases (ETERNITY) project is actively addressing this challenge. With an ambitious goal of understanding how brain metabolic pathways respond to physiological and pathological stimuli, ETERNITY is working to identify new metabolic targets as a foundation for future personalized therapies. Tackling these complex issues requires strong collaboration between academia and industry, and ETERNITY is fostering precisely this environment.
Through its interdisciplinary and intersectoral approach, the project is already generating valuable insights into the mechanisms underlying impaired brain metabolism. By leveraging the complementary expertise of its partners, ETERNITY will also identify novel pharmaceutical targets and developing potential nutritional interventions. Beyond research, the project is strengthening European innovation capacity by training a new generation of researchers who are gaining firsthand experience in academia, the pharmaceutical sector, and the food supplement industry.
Doctoral Candidates (DCs) within ETERNITY are being equipped with cutting-edge methodological skills, innovation-driven thinking, and transferable competencies essential for impactful careers in both research and industry. As the project progresses, its collaborative efforts and training initiatives will contribute to one of the greatest societal challenges of our time: promoting brain health during ageing and delaying the onset of neurodegenerative diseases.
All Doctoral Candidates (DCs) were recruited on schedule and are actively contributing to the project’s scientific objectives. The originally planned experiments have either been completed or are currently in progress, with significant advancements in the development and implementation of experimental protocols. Preliminary data have been successfully collected, addressing the three core research objectives:
- Dissecting energy metabolism pathways in different brain cell types under physiological conditions, during ageing, and in response to specific diets (Milestone 7).
- Identifying altered metabolic pathways in Alzheimer’s disease (AD) (Milestone 8).
- Designing and testing interventional strategies to counteract metabolic dysfunction in age-related disorders (Milestone 9).
Key technical achievements include the refinement of methodologies, optimization of experimental workflows, and generation of datasets critical to addressing these objectives. Additionally, the DCs have undergone targeted scientific training, enhancing their technical expertise and methodological competencies.
Project governance and data management have also progressed, with the establishment of essential documents: the Supervisory Board operational framework (Deliverable 29), the Data Management Plan (DMP) (Deliverable 25), and the Personal Career Development Plans (PCDPs) for each DC (Deliverable 26). Furthermore, the first-year progress report (Deliverable 30) was successfully submitted to REA, summarizing the project's initial implementation phase.
- Dissecting energy metabolism pathways in different brain cell types under physiological conditions, during ageing, and in response to specific diets (Milestone 7).
- Identifying altered metabolic pathways in Alzheimer’s disease (AD) (Milestone 8).
- Designing and testing interventional strategies to counteract metabolic dysfunction in age-related disorders (Milestone 9).
Key technical achievements include the refinement of methodologies, optimization of experimental workflows, and generation of datasets critical to addressing these objectives. Additionally, the DCs have undergone targeted scientific training, enhancing their technical expertise and methodological competencies.
Project governance and data management have also progressed, with the establishment of essential documents: the Supervisory Board operational framework (Deliverable 29), the Data Management Plan (DMP) (Deliverable 25), and the Personal Career Development Plans (PCDPs) for each DC (Deliverable 26). Furthermore, the first-year progress report (Deliverable 30) was successfully submitted to REA, summarizing the project's initial implementation phase.
The ETERNITY project is advancing the understanding of how metabolic dysfunction contributes to aging and age-related disorders. Research on brain energy metabolism has provided key insights into the metabolic regulation of neurons and microglia, revealing sex-specific adaptations and mitochondrial dynamics in response to diet and aging.
Further efforts have focused on identifying metabolic pathways altered after synaptic stimulation in vitro and in vivo, paving the way for future experiments in Alzheimer’s disease models. These studies aim to characterize metabolic disruptions and assess their potential as therapeutic targets. In parallel, the project has made significant progress in developing interventional strategies for age-related metabolic dysfunctions. A novel CAR-T cell system targeting senescent cells demonstrated selective cytotoxicity, presenting a promising senotherapeutic approach. A surfaceome analysis also identified unique surface proteins in senescent cells as potential therapeutic targets.
Long-term in vivo studies have explored diet-based interventions, comparing ad libitum and time-restricted feeding under standard or high-fat diet conditions. Findings suggest that time-restricted feeding preserves cognitive function during senescence, independent of diet, and improves glucose metabolism, even surpassing control diet groups. Furthermore, analysis of metabolic markers revealed shifts in ketone metabolism and fatty acid oxidation-related gene expression patterns, confirming diet-induced metabolic adaptations.
The outcomes of the ETERNITY project have strong translational potential, offering novel therapeutic targets and dietary interventions to mitigate cognitive decline and metabolic dysfunction in aging and neurodegenerative diseases. Further research will focus on validating metabolic targets in preclinical neurodegeneration models, expanding interventional strategies, and identifying potential human biomarkers for early detection and personalized treatments. Regulatory and commercialization pathways will also be explored, including patent protection for potential drug targets and collaborations with the pharmaceutical and nutraceutical industries. International partnerships will be sought to advance clinical validation and ensure the successful translation of findings into real-world applications.
By integrating fundamental research with translational applications, the ETERNITY project is poised to contribute significantly to the fight against neurodegeneration and to foster the development of innovative therapeutic solutions for aging populations.
Further efforts have focused on identifying metabolic pathways altered after synaptic stimulation in vitro and in vivo, paving the way for future experiments in Alzheimer’s disease models. These studies aim to characterize metabolic disruptions and assess their potential as therapeutic targets. In parallel, the project has made significant progress in developing interventional strategies for age-related metabolic dysfunctions. A novel CAR-T cell system targeting senescent cells demonstrated selective cytotoxicity, presenting a promising senotherapeutic approach. A surfaceome analysis also identified unique surface proteins in senescent cells as potential therapeutic targets.
Long-term in vivo studies have explored diet-based interventions, comparing ad libitum and time-restricted feeding under standard or high-fat diet conditions. Findings suggest that time-restricted feeding preserves cognitive function during senescence, independent of diet, and improves glucose metabolism, even surpassing control diet groups. Furthermore, analysis of metabolic markers revealed shifts in ketone metabolism and fatty acid oxidation-related gene expression patterns, confirming diet-induced metabolic adaptations.
The outcomes of the ETERNITY project have strong translational potential, offering novel therapeutic targets and dietary interventions to mitigate cognitive decline and metabolic dysfunction in aging and neurodegenerative diseases. Further research will focus on validating metabolic targets in preclinical neurodegeneration models, expanding interventional strategies, and identifying potential human biomarkers for early detection and personalized treatments. Regulatory and commercialization pathways will also be explored, including patent protection for potential drug targets and collaborations with the pharmaceutical and nutraceutical industries. International partnerships will be sought to advance clinical validation and ensure the successful translation of findings into real-world applications.
By integrating fundamental research with translational applications, the ETERNITY project is poised to contribute significantly to the fight against neurodegeneration and to foster the development of innovative therapeutic solutions for aging populations.