Clinical and environmental factors, functional status and multimorbidity: Stratifying progression and prognosis of diseases, frailty and disability

Leader: Fabrizia​ Lattanzio, INRCA
Co-Leader: Francesco Landi, UNICATT


Spoke Themes

This Spoke addresses the clinical complexity and heterogeneity of older subjects’ phenotype using an interdisciplinary and lifelong approach. Spoke 3 will contribute to the formulation of a methodological framework to evaluate environmental, biological, clinical and functional components in age-related diseases, multimorbidity and frailty, and their role in identifying risk stratification strategies to be used in interventional studies. The Spoke adopts an innovative approach including technological and Artificial Intelligence assets integrated within the Age-It consortium.


Activities are organised around 6 WPs: WP1 is cross-cutting as it defines the methodological framework; WP 2-3-4-5 study age-related diseases in relation to multimorbidity and frailty, focusing on defining the role of biomarkers, risk stratification, management strategies. WP6 is specifically dedicated to determining the impact of climate change and pollution on Ageing.


Geriatria, gerontologia, neurologia, cardiologia, reumatologia, endocrinologia, ortopedia, biologia, epidemiologia, nefrologia, immunologia, medicina interna nonché statistica e informatica. 

Work Packages

Prof. Nicola Ferrrara, UNINA

WP1 focus on: 1) longitudinal data exploitation and collection (surveying and harmonizing existing longitudinal cohort data for a multidimensional assessment of age-related diseases, multimorbidity and frailty and related outcomes; conceptualising new longitudinal data collections in suitable population cohorts at high-risk of adverse outcomes); 2) assessing gender-sensitive domains (sex, identity, roles, relations, institutionalized, social, behavioural) as modifiers of multimorbidity outcomes; 3) designing and implementing educational programmes on ageing (e.g., Ph.D. Ageing School: Pathophysiology of and prevention of frailty and disability among older adults – AgingPath).

Prof. Carlo Pappone, UNISR

WP2 will consider specific age-related conditions, such as chronic musculoskeletal diseases, neurodegenerative, cardiometabolic disorders, cardio-vascular diseases and sarcopenia with the aim to provide early diagnosis, better assessment or accurate monitoring in patients with multimorbidity and frailty.

Prof Stefano Salvioli, UNIBO

WP 3 will focus on understanding the role of biomarkers to: 1) better characterize multimorbidity, frailty and disability phenotypes; 2) improve diagnosis and prognosis; 3) support effective treatment strategies identification. Moreover, it applies AI techniques – in close collaboration with Spokes 5 and 9 – to develop biomarker-based multiparametric predictive algorithms and support optimal clinical use of existing, innovative and novel biomarkers in multimorbid older patients.

Prof. Rosa Liperoti, UNICATT

WP4 aims at effectively stratifying risks related to multimorbidity, frailty and disability through the use of advanced statistical and AI techniques to: 1) assess the risk of adverse cognitive and functional outcomes; 2) unveil the existence of clusters of diseases; 3) unveil bidirectional cross-linking between functional dimensions and multimorbidity and their longitudinal trajectories. Finally, it includes tasks to design and validate assessment tools by integrating biomarkers and other multidimensional factors.

Prof. Antonio Cherubini, INRCA

WP5 will offer optimal management strategies for multimorbid older patients, along the three axes of socioeconomic, medical and technological assessments. Tasks include: 1) designing appropriate interventions for delay progression or improve prognosis; 2) defining risk groups considering cognitive and functional interactions, key mediators of inflammation, nutritional factors and frailty; 3) implementing proof of concepts and/or pilot studies to assess the feasibility of innovative multidisciplinary stratified care pathways.


Prof. Licia Iacoviello, NEUROMED

WP6 focus on enquiring the impact of Climate Change and pollution on: 1) clinical and functional trajectories; 3) clinical outcomes; 2) clusters of age-related conditions, multimorbidity and their complex dynamic interactions. The WP ultimate aim is to drive strategic recommendations for communities and policy makers – in close collaboration with Spoke 10 – to build resilience against climate changes and pollution in the older population.

Key Outputs

  • National PhD Programme proposal (WP1). The PhD will provide expertise on the molecular and cellular mechanisms that determine longevity and healthy aging, seeking new therapeutic targets and new solutions as well as a broader understanding of «Ambient Assisted Living».  

  • Sviluppare nuove metodologie per lo studio di specifiche condizioni associate all’età nei pazienti anziani con multimorbilità e fragilità

  • Overview of the research activities on selected biomarkers (WP3). The following soluble biomarkers of aging in frailty and multimorbidity have been identified: GDF15, FGF21, NfL and RAGE. Now the analyses are starting. A review paper on selected biomarkers of aging in frailty and multimorbidity has been submitted.

  • La progettazione di nuovi interventi e strategie mirate negli anziani con multimorbilità

  • Creare nuove evidenze sul rapporto del cambiamento climatico e dell’inquinamento sulla salute degli anziani

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