Microgravity-induced stress mechanisms in human stem cell-derived cardiomyocytes
Aviseka Acharya, Harshal Nemade, Symeon Papadopoulos, Jürgen Hescheler, Felix Neumaier, Toni Schneider, Krishna Rajendra Prasad, Khadija Khan, Ruth Hemmersbach, Eduardo Gade Gusmao, Athanasia Mizi, Argyris Papantonis, Agapios Sachinidis
Abstract
Exposure to outer space microgravity poses a risk for the development of various pathologies including cardiovascular disease. To study this, we derived cardiomyocytes (CMs) from human-induced pluripotent stem cells and exposed them to simulated microgravity (SMG). We combined different "omics" and chromosome conformation capture technologies with live-cell imaging of various transgenic lines to discover that SMG impacts on the contractile velocity and function of CMs via the induction of senescence processes. This is linked to SMG-induced changes of reactive oxygen species (ROS) generation and energy metabolism by mitochondria. Taken together, we uncover a microgravity-controlled axis causing contractile dysfunctions to CMs. Our findings can contribute to the design of preventive and therapeutic strategies against senescence-associated disease.