Age-related lung diseases: Modeling the development without animal experiments
COPD or pulmonary fibrosis - many chronic lung diseases develop in old age or worsen drastically in later life. Which molecular processes play a role here? Dr. Mareike Lehmann, project lead in the Lung Repair and Regeneration Unit (LRR) at the DZL site in Munich (CPC-M), is investigating these processes using an innovative approach:
How can the development of lung diseases in ageing cells be understood without having to resort to animal experiments?
For this forward-looking project, Mareike Lehmann has now received funding from the German Centre for Risk Assessment (BfR), which explicitly supports projects that reduce animal experiments. With 240,000 euros over three years, she has already been able to recruit a doctoral student for the project, and the first experiments have started in spring 2020.
The basic problem: what exactly happens in an ageing human lung is still largely unknown. Which processes lead to which deterioration? What could stop them? So far, this has mostly been investigated in animal models, mainly mice. Which leads to multiple problems and challenges:
- The mouse does not show many age-related pathologies such as neurodegenerative diseases or chronic lung diseases in old age.
- The results can only insufficiently be transferred to processes in human cells
- The CPC-M and biomedical science in general is trying to reduce animal experimentation
Mareike Lehmann has therefore launched a project that adresses all three challenges: A model of the ageing human lung will be generated from different samples of human lung tissue (Precision Cut Lung Slices). To do this, she irradiates the lung slices and thus initiates an artificial ageing process (cellular senescence). These lung cells that have aged outside the body can then be tested in real time for:
- Molecular processes of cellular aging
- Characteristic changes in chronic lung diseases such as scarring of the lung tissue or destruction of alveolar cells
This method of artificially ageing lung cells will now be established first. The ultimate goal: to understand what happens in the ageing lung: What mechanisms lead to lung diseases such as COPD or pulmonary fibrosis? And of course: How can we reverse or prevent these ageing processes?