Microgravity-induced stress mechanisms in human stem cell-derived cardiomyocytes

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. [Display omitted] •Simulated microgravity (SMG) causes ROS production in human cardiomyocytes (CMs)•SMG inhibits mitochondria function and energy metabolism and induces senescence of CMs•SMG attenuates contractile velocity, beating frequency and Ca2+ influx in CMs•SMG induces chromosomal changes and modifies the chromosomal architecture in CMs Biological sciences; Molecular biology; Cell biology; Stem cells research