Slowing Immune system Ageing through Dietary control

ImmunAgeD

About this project

Hypothesis

Immune ageing processes, characterised by both suppressed (immunosenescence) and exaggerated (inflammaging) immune responses, are crucial to organ aging. It has been suggested that both genetic susceptibility, as well as environmental factors (diet, pollution, lifetime exposure to infectious agents and other proinflammatory stimuli) are responsible for sustaining immune ageing, however with insufficient data so far documented.1–3
 
Based on the latest Eurostat estimates in 2021, individuals living in the European Union (EU) aged 65 and over accounted for 20.9% of the total population at that time. This segment of the population will grow steadily over the next 30 years, reaching 30.0% of the EU population in 2055. In the same context, the World Health Organization (WHO) defines a new parameter – healthy life expectancy (HALE), indicating the the average number of years, starting from birth, which a person is expected to live in `full health’, emphasising the need for interventions meant to reduce overall morbidity. Romania’s elderly population reached 19.5% in 2021, and was ranked as one of the European countries with the lowest HALE values, with an average of 66.8 years in 2019. 4–6
 
ImmunAgeD (2023-2026) is positioned at the intersection between the ageing trajectory of Europe’s population and an ever increasing morbidity, aspects which are also reflected in the population of our country. These overlapping figures highlight the necessity for uncovering the determining factors and processes involved, with a view to devise interventions designed to limit these conditions, in the context of immune ageing. 7

Objectives

The overall objective of the project is to describe the genetic and environmental factors, which influence the physiological ageing of the immune system.
The specific objectives of ImmunAgeD include:
1. Evaluating immune and epigenetic profiles in a diverse Romanian population with individuals of different ages, from rural and urban backgrounds, with different dietary habits;
2. Studying the impact of traditional Romanian fasting, when compared to a Western diet, on immune and epigenetic ageing scores in a cross-sectional study;
3. Studying the effect of traditional Romanian fasting on immune and epigenetic ageing scores in a longitudinal study.

The ImmunAgeD project will integrate state-of-the-art molecular technologies (epigenomics, transcriptomics, proteomics and metabolomics) with functional immunological assays and cutting-edge systems biology approaches to characterise the factors influencing immune ageing in the Romanian population. We will use these technologies to calculate immune ageing scores and their association with chronological age, body fitness and comorbidities. ImmunAgeD includes 120 subjects participating in the cross-sectional substudy, and an estimated 500 patients, representing the cohort explored longitudinally, formerly enrolled as healthy controls in the FUSE study.

The novelty of our approach lies in the elaboration of a methodology which can be used for the early detection of age-related clinical phenotypes, using immune phenotyping and methylation techniques for the calculation of an epigenetic clock. Also, this project will investigate the potential to modify immune-mediated ageing by dietary interventions. ImmunAgeD will also allow us to assess the role of a changing social landscape, as the Romanian population shifts from a traditional to a more Western type of diet and lifestyle.

1.     López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Hallmarks of aging: An expanding universe. Cell 186, 243–278 (2023).
2.     Accardi, G. & Caruso, C. Immune-inflammatory responses in the elderly: an update. Immun. Ageing A 15, 11 (2018).
3.     Franceschi, C. & Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A. Biol. Sci. Med. Sci. 69 Suppl 1, S4-9 (2014).
4.     EUROSTAT. Ageing Europe. Ageing Europe https://ec.europa.eu/eurostat/cache/digpub/ageing/.
5.     GHO | Global Health Observatory Data Repository (European Union) | Healthy life expectancy (HALE) – Data by country. WHO https://apps.who.int/gho/data/node.main-eu.HALE?lang=en.
6.     Healthy life expectancy (HALE) at birth (years). https://www.who.int/data/gho/data/indicators/indicator-details/GHO/gho-ghe-hale-healthy-life-expectancy-at-birth.
7.     Franceschi, C. et al. The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front. Med. 5, 61 (2018).

Teams

Our research team at the Medical Genetics Department of UMF Cluj-Napoca studies the mechanisms of inflammatory diseases and their interrelationship with individual genetic susceptibility factors. We are curious how the variance in our genome or epigenome can alter the immunological processes and cause inflammatory disease. We assess immunological functions of primary cells in patient cohorts and in controls and we use multi-omics to assess the different molecular layers that can contribute to inflammatory dysregulation. Currently, we are investigating the mechanisms of immune memory associated to long term proinflammatory effects and accelerated immunological aging in gout, hyperuricemia, systemic sclerosis and other autoinflammatory and autoimmune disorders.

Craiova Human genomics

Cluj Functional Genomics

Cluj Medical Genetics

Cluj Rheumatology

Cluj Infectious Diseases

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