Today, we are facing an increasing burden of functional decline and disease in the ageing population, for which treatment options still remain discouraging. This is partly due to the complex involvement of genetic and environmental factors. One example is ionizing radiation, which is suggested to induce ageing through DNA damage, oxidative stress and chronic inflammation, and proposed to accelerate the onset of Alzheimer's disease (AD). This might be particularly important for children exposed to cranial radiotherapy, being most prone to long-term cognitive sequelae. Furthermore, a possible risk for ageing is also of concern for astronauts, being exposed to a multitude of stressors including cosmic radiation, reduced gravity and psychological stress. Yet, many health aspects, including ageing, still remain unexplored. A better understanding of ageing in response to different stressors is thus essential, which requires suitable experimental models both in a clinical and space-flight setting. Our goal is to address this need, through implementation of appropriate in vitro and in vivo set-ups.
Firstly, we developed in vitro and in vivo approaches to study brain ageing and neurodegeneration in response to irradiation and psychological stress. Hereto, we optimized an in vitro ageing model using mouse primary neurons, in which we could characterize neuronal ageing by measuring calcium-fluxes, synaptic communication, oxidative stress and senescence, and define AD pathology. Furthermore, we use an AD mouse model (3xTg) showing signs of brain ageing and AD pathology within 3-12 months, which we use as a read-out for premature ageing and AD following exposure to different stressors.
Secondly, we envision to induce accelerated ageing by subjecting cells to simulated space conditions. For this, our lab is experienced in exposing different human and murine cell types (fibroblasts, blood cells, immune cells, muscle cells and neurons) to simulated microgravity using the random positioning machine, followed by appropriate cellular and molecular analysis tools.
In all, our goal is to gain a better insight in human ageing and the importance of environmental factors that might trigger the onset of age-related diseases. For this, we developed a multifactorial approach which can be applicable for a range of stressors that are of interest in the context of ageing research.
Acknowledgements: Belspo/Prodex program (C4000109861) and Meabco A/S for financial support