Gut-brain-axis: Targets for improvement of cognition in the elderly

Project Information

SmartAge

Grant agreement ID: 859890

DOI

10.3030/859890

Project closed

EC signature date 22 June 2020

Start date 1 September 2020

End date 28 February 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 3 946 980,96

EU contribution

€ 3 946 980,96

Coordinated by

UNIVERSITATSKLINIKUM JENA
Germany

Periodic Reporting for period 2 - SmartAge (Gut-brain-axis: Targets for improvement of cognition in the elderly)

Reporting period: 2022-09-01 to 2025-02-28

Summary of the context and overall objectives of the project

Currently, no cure exists to prevent progression from mild cognitive impairment to dementia. This pressing societal challenge has long been understudied. SmartAge addressed this gap by exploring the gut-brain axis and its influence on cognition during aging, with the aim to identify novel diagnostic and therapeutic strategies. Concurrently, SmartAge responded to the growing demand for specialists in this interdisciplinary field.
The main objectives were in short:
• Investigate gut-brain interactions in aging via hypotheses on inflammaging, intestinal permeability, and immune responses.
• Identify microbiome-based targets for diagnostic and therapeutic development to improve cognitive health.
• Train early-stage researchers in designing and conducting lifestyle and nutritional interventions.
• Educate a new generation of interdisciplinary scientists skilled in gut-brain communication in aging.
Conclusion of the action:
SmartAge effectively delivered on its dual mission: advancing scientific understanding of gut–brain interactions in aging and establishing a high-quality training environment for early-stage researchers. The project implemented an innovative and coherent research programme across multiple disciplines, resulting in a shared knowledge base, enduring collaborations, and capacity-building within and beyond academia.
The structured integration of fundamental science, technology development, and translational perspectives ensured that SmartAge not only contributed to answering key research questions but also positioned its outputs for future exploitation in clinical and societal contexts. The consortium maintained strong coordination, met all planned milestones, and fostered a culture of open communication and knowledge exchange.
Through its inclusive outreach activities, SmartAge also promoted public engagement with brain and gut health, supporting a broader impact beyond the scientific community. As a result, the project leaves behind a legacy of new insights, validated platforms, trained experts, and stakeholder networks that will continue to drive innovation in cognitive aging research.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Since its start in September 2020, SmartAge built a robust research and training framework, integrating 15 doctoral projects across Europe. During the first period, key milestones such as ESR recruitment and network-wide training activities were completed. By the second period, ESRs had finalized or submitted their theses, and project-wide deliverables and milestones were successfully achieved.
Scientific breakthroughs include:
• Mechanistic and cross-species evidence linked inflammaging, gut barrier dysfunction, and microbiota alterations to cognitive decline in aging.
• Key microbiome-related discoveries included specific microbial species and metabolites linked to cognitive function (e.g. phenylalanine and glutamate pathways, bile acids, SCFA, butyrate-producing and glutathione production species).
• Validation of non-pharmacological (e.g. mediterranean diet, physical activity) and pharmacological (e.g. metformin) interventions in preclinical and clinical settings.
• Characterization of the role of Nod1, serum ferritin, and specific bacterial strains (e.g. Gemmiger formicilis) in cognitive function.
• Multi-omics multi-organs analyses identify critical host–microbiome co-metabolites and pathways across human and murine studies.
• Integration of microbiome and diet data into whole-body metabolic models (Persephone and Nutrition toolbox).
• A gut-on-a-chip platform enabled real-time monitoring of intestinal barrier integrity
• BrainAGE was established as a sensitive biomarker for brain aging.
• Completion of all ESR projects and outreach via public events and communication activities.
Dissemination and exploitation:
SmartAge results were shared through almost 100 scientific presentations, >50 outreach activities (e.g. Science Nights, podcasts), and over 50 peer-reviewed publications.
Core outputs include:
• Open-access multi-omics datasets and analysis pipelines.
• A shared mouse/human biobank.
• A gut-on-a-chip platform intended for patent application.
• Intervention packages (e.g. online-guided physical activity) ready for use in future clinical trials.
The scientific, translational, and educational activities established SmartAge as a benchmark for interdisciplinary research on cognitive aging.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

SmartAge significantly advanced the state of the art by combining molecular, clinical, and computational research across species and disciplines. Key advances include:
• Novel mechanistic insights: Cognitive decline was shown to be modulated by gut microbiota and virome composition, immune signalling, and gut permeability.
• Innovative technologies: A gut-on-a-chip system enabled real-time monitoring of barrier integrity. The BrainAGE score proved sensitive to intervention effects in humans.
• New therapeutic targets: Specific bacterial strains, metabolites and metabolic pathways were identified as modulators of cognition.
• Translational impact: Clinical feasibility of metformin, dietary interventions, and tailored physical activity programs was demonstrated.
• Systems biology: Personalized whole-body models integrate host–microbiome metabolism and support precision nutrition and cognition research.
Socio-economic and societal implications:
• The project contributes to delaying cognitive decline in aging, addressing a major public health concern.
• By training ESRs and building interdisciplinary capacities, SmartAge strengthens Europe’s innovation potential in brain and microbiome research.
• Tailored communication strategies and outreach activities promoted healthy aging across diverse European populations.
• SmartAge successfully combined fundamental research, technological development, clinical application, and societal outreach—paving the way for future innovations in cognitive health.

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