We will analyze senescence-associated changes in the lysosomal-mitochondrial axis. In this context, we will also study mechanisms of mitochondrial quality control in senescent cells in collaboration with the group of Corina Madreiter-Sokolowski.

In collaboration with Corina Madreiter-Sokolowski and Markus Schosserer we will apply state of the art microscopical techniques to study alterations of the lysosomal membrane in senescence models, complemented with studies using high-pressure freezing EM allowing an unprecedented insight in changes of lysosmal membrane in senescent cells (Collaboration with Lukas Huber, Medical University of Innsbruck). We will investigate changes in mitochondrial metabolism in senescent cells, to determine novel mechanisms of metabolic rewiring during senescence.

We plan to validate mechanisms of cellular senescence identified in 2D cell culture models in quasi-physiological organoid models for photoaging of the skin. Among others, we will study UVB-induced molecular alterations in skin equivalents and use senoskin models for the validation of candidate senolytic compounds. Finally, we will evaluate the potential of candidate senolytic compounds in ex vivo skin in collaboration with external partners (Dermatology Dept. Of University of Ulm, Germany and Oriflame AB, Stockholm, Sweden) for testing new products for skincare and the prevention/ treatment of skin diseases.

We will develop and validate senolytics related to senescence-associated changes in the lysosomal-mitochondrial axis. Based on preliminary results, we aim to develop new molecules with increased and highly specific senolytic activity. In collaboration with Markus Schosserer the most promising compounds for senolysis will be evaluated in a mouse model in vivo.

In this project, one of our well-trained PhD students and a technician, together with dedicated MSc students, will conduct the experiments. Furthermore, the PhD student will join the laboratory of Carina Madreiter-Sokolowski in Graz to learn and apply advanced technologies to determine ROS production in cellular senescence. The PhD student will also study mechanisms and histopathology of skin aging (secondment to the laboratory of Karin Scharffetter-Kochanek, Dermatology Dept. of University of Ulm, Germany) and work with well-established ex vivo skin models for testing new products for skincare (secondment to the Skin Research Laboratory of Oriflame AB, Stockholm, Sweden).