Iron as a driver of fibrosis and regeneration

Projektinformationen

IRONAGE

ID Finanzhilfevereinbarung: 794744

DOI

10.3030/794744

Projekt abgeschlossen

EK-Unterschriftsdatum 23 Februar 2018

Startdatum 1 April 2018

Enddatum 26 Mai 2020

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 158 121,60

EU-Beitrag

€ 158 121,60

Koordiniert durch

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Spain

Periodic Reporting for period 1 - IRONAGE (Iron as a driver of fibrosis and regeneration)

Berichtszeitraum: 2018-04-01 bis 2020-03-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The European Commission projects that the ratio of the very elderly population (above 80 years) will more than double in the EU over the next fifty years. Healthcare and long-term care expenditures are expected to rise due to the increase in the prevalence of aging associated diseases. Among the top of the list in aging associated diseases are fibrotic diseases. Estimates are that fibrotic diseases cause one third of the death cases in the EU.
Fibrotic diseases originate from scar formation in the internal organs. As the scar tissue progressively grows, it impedes the function of the organ, and leads to a decline in health. The incidence of fibrotic diseases increases with age exponentially. Fibrosis can affect many organs. Fibrotic scars can form in the heart leading to cardiac arrest, lung fibrosis leads to a decline in respiratory capacity, and fibrosis in the kidneys or in the liver lead to a general health decline. Fibrotic diseases to date have no cure, and this is because of the limited understanding of their pathobiology.
The overall objective of this action was to investigate the biology that links fibrotic diseases to aging.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Physiological ageing is associated with a decline in the ability of the human body to heal itself by replacing damaged cells or tissues for healthy ones. As a result, elderly accumulate damaged cells and scar tissues that medically manifest as fibrosis. The causes for aging associated cellular damage and for the declining regenerative capacity in the elderly are mostly unclear. Recent genetic studies found a striking correlation between iron availability in the body and healthy aging. Individuals with a better capacity to deal with excess iron were found to be more likely to age in a healthy way, and to live particularly long lives. Iron is an essential element for cellular respiration and for blood formation. Iron deficiency causes low red blood cell count (anemia), and fatigue. However, too much iron can be toxic to cells. Damaged cells for unknown reasons accumulate iron. Iron accumulation also occurs on the level of the body throughout aging. However, whether iron accumulation can be causatively linked to aging associated phenomena, such as cellular damage and fibrosis, remains unclear.
The central hypothesis of this action was that there is a causative link between free-iron levels, cellular damage and fibrosis. This action experimentally addressed whether patients with fibrotic diseases are more likely to have altered iron levels, whether iron levels can be made accountable for aging associated cellular damage, and fibrosis, and whether lowering iron levels can prevent fibrosis.
This action found that fibrotic tissues from various organs present with iron accumulation. Free iron levels have a clear causative role in fibrotic disorders. Increased iron levels are sufficient to explain aging associated cellular damage. Modulating iron levels can prevent fibrosis formation.
The findings of this action have been presented to the international scientific community on several conferences. The manuscript summarizing the results of this action is currently in preparation. Building on these findings the fellow is currently in the process of applying for independence in order to establish his own laboratory.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Fibrotic disorders increase in incidence exponentially throughout aging. As of today, it is estimated that fibrotic diseases account for one third of the death cases in the EU. With the aging of the societies in EU countries, it is projectable that the health burden that fibrotic diseases pose will progressively increase over the coming years. Therefore, it is essential to understand what links aging to increased incidence in fibrotic diseases and to explore new ways how to prevent this from happening, and thereby secure healthy aging.
The findings of this action suggest a causative connection between the aging associated iron accumulation and the rising incidence of fibrotic diseases with age. The action shows that preventing iron levels from rising can be effective in some models to prevent fibrosis formation. The fellow will pursue this connection between iron and fibrotic diseases in his future lab with the aim to explore novel diagnostic, preventative and therapeutic regimen for fibrotic diseases.

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