Decode the Immunoscience of age-related diseases

About this call

Expected Impact:

The action under this topic is expected to achieve the following impacts:

Accelerate EU access to more cost-effective interventions in an increasingly ageing population by identifying personalised treatment approaches for elderly-onset immune diseases.

Decrease disease risk later in life by defining specific prevention strategies based on ageing biomarkers and risk factors.

Halt age-associated disease exacerbation by the identification of predictive and digital biomarkers that can stratify patients for early intervention.

Improve quality of life for healthy individuals and patients by preventing further health decline, avoiding escalating care costs, and properly stratifying individuals earlier in the diagnostic pathway.

Accelerate adoption of innovative diagnostic, preventative, and therapeutic strategies, strengthening the EU’s position as a healthcare innovator.

Evaluate digital biomarker as potential regulatory endpoints in the ultimate goal to develop medicines for ‘healthy ageing’.

Integrate fragmented research efforts by bringing together health industry sectors and stakeholders to develop clinical and multi-omics data integration capabilities.

Enable new data-driven research by building AI infrastructure on existing data and cohorts that no single organisation could develop independently

Patients and citizens will benefit from improved medical practice and healthcare solutions, new targeted prevention strategies and ultimately healthier ageing.

The action will support EU policy and priorities including the European Health Data Space Regulation (EHDS) and the EU Artificial Intelligence Act, while contributing to European competitiveness in addressing one of society's major challenges.

Expected Outcome:

The action under this topic must contribute to all of the following outcomes:

Researchers will benefit from a better understanding of the potential causal links between chronic inflammatory diseases and biological ageing , and the predictiveness of the accompanying biomarkers could allow for the definition of precise risk profiles for age-associated immune disease onset and exacerbations.

Patients will benefit from new early detection strategies as well as new diagnostic approaches to differentiate disease onset in elderly people from onset in younger adults . This will inform a personalised medicine approach to treatment and will in turn help to prevent disease progression.

Patients and healthcare professionals will benefit from the repurposing or development of novel therapies for ageing populations with chronic inflammatory diseases and precision medicine approaches that prevent health decline while reducing healthcare costs.

Researchers and industry will benefit from the establishment of systematic collaborative approaches for the use of available biobanks across age ranges , immune diseases and comorbidities to adopt innovative approaches (by integration of multi-omics, immunophenotyping, digital biomarkers, ageing clocks, and artificial intelligence (AI) with comprehensive patient information).

Patients and healthcare professionals will benefit from deeper insights into treatment response and the evaluation of the impact of ageing on treatment effectiveness.

Industry and researchers will benefit from the establishment of regulatory pathways for novel intervention strategies and biomarkers , leading to the faster clinical development of drugs that improve age-associated disease exacerbations, ultimately enabling the translation of research findings into therapeutic solutions for vulnerable patient populations. This includes the field of digital biomarkers and their use in monitoring activity, strength and fatigue as exemplary readouts.

Scope:

The global population is undergoing an unprecedented demographic shift, with the number of individuals aged 65 and older projected to double by 2050, presenting one of the most significant public health challenges of our time. The transition to an ageing society is accompanied by a parallel rise in the prevalence of chronic diseases, multimorbidity, and years lived in poor health, placing immense strain on healthcare systems worldwide [1] . Central to this phenomenon is the progressive decline of immune function with age which not only increases susceptibility to infections and malignancies, but also drives chronic low-grade inflammation, known as "inflammaging" [2] .

The profound age-related changes to the immune system are collectively termed immunosenescence. These changes include thymic involution, reduced naive T-cell production, expansion of memory T-cells with limited repertoire diversity, increased inflammatory cytokine production (inflammaging), and broad dysregulation of innate immunity [3] [4] . In parallel, senescent cells accumulate and secrete SASP cytokines—such as IL‑6, IL‑1β, and TNF—which further amplify inflammaging and contribute directly to age‑related immune dysfunction [5] [6] . Concurrently, there is a rising incidence of immune-mediated diseases with initial onset in elderly populations, including late-onset rheumatoid arthritis [7] , elderly-onset inflammatory bowel disease (IBD) [8] , late-onset systemic lupus erythematosus (SLE) [9] and late-onset respiratory diseases [10] [11] .

Critically, advanced age is associated with the increased incidence of autoimmune and inflammatory diseases [12] . Moreover, older adults exhibit heightened vulnerability to immune-mediated pathologies ranging from late-onset autoimmune disorders to vaccine hyporesponsiveness and impaired tissue repair [13] [14] . Despite the clear clinical burden, the mechanistic underpinnings of how ageing reshapes immune homeostasis and disease susceptibility, and concomitantly, of how diseases reshape the ageing-process and the immune system, remain incompletely understood. A comprehensive understanding of the bidirectional relationship between immune system dysfunction and the ageing process is therefore imperative to develop targeted interventions that can prevent, delay, or reverse age-associated immune diseases and ultimately extend health span.

Despite their clinical significance, elderly-onset immune diseases remain poorly understood compared to their younger adult-onset counterparts. Evidence suggests that they may represent distinct disease entities with unique pathogenic mechanisms, clinical presentations, and treatment responses [15] [16] . The intersection of immunosenescence with pathological immune dysregulation presents both challenges and opportunities for targeted interventions.

Industry, regulators, researchers, and other stakeholders should address the critical gap in our understanding of how ageing-related immune changes contribute to disease pathogenesis in the elderly. New evidence-based findings should help to elucidate the molecular drivers of both elderly-onset immune diseases as well as immune disease exacerbations during ageing. In addition, these findings should help to identify predictive biomarkers, leading to age-appropriate therapeutic and prevention strategies accounting for the unique immunological context of older patients, and ultimately reducing the socio-economic burden for society.

The action funded under this topic therefore aims to elucidate the key biological determinants that drive healthy ageing and immune‑mediated disease, with a particular focus on how age‑associated immune system remodelling shapes these outcomes.

Applicants are expected to address all of the following objectives of the topic in their proposal:

Understanding molecular and clinical differences between younger adult-onset and elderly-onset diseases : The focus of the action should be on immune-mediated diseases with a peak of onset in elderly patients, such as inflammatory bowel disease and respiratory diseases, and specifically directed to diseases with mainly elderly onset.

Therefore, in summary the proposal should cover the following immune-mediated diseases: