Humans are constantly exposed to ionizing radiation deriving from outer space sources or activities related to medical care. Absorption of ionizing radiation doses over a prolonged period of time can result in oxidative damage and cellular dysfunction inducing several diseases, especially in ageing subjects. In this report, we analyze the effects of ionizing radiation, particularly at low doses, in relation to a variety of human pathologies, including cancer, and cardiovascular and retinal diseases. We discuss scientific data in support of protection strategies by safe antioxidant formulations that can provide preventive or potential therapeutic value in response to long-term diseases that may develop following exposure.

Microgravity (µG) experienced during space flights promotes adaptation in several astronauts’ organs and tissues, with skeletal muscles being the most affected. In response to reduced gravitational loading, muscles (especially, lower limb and antigravity muscles) undergo progressive mass loss and alteration in metabolism, myofiber size, and composition. Skeletal muscle precursor cells (MPCs), also known as satellite cells, are responsible for the growth and maintenance of muscle mass in adult life as well as for muscle regeneration following damage and may have a major role in µG-induced muscle wasting. Despite the great relevance for astronaut health, very few data are available about the effects of real µG on human muscles. Based on the MyoGravity project, this study aimed to analyze: (i) the cellular and transcriptional alterations induced by real µG in human MPCs (huMPCs) and (ii) the response of human skeletal muscle to normal gravitational loading after prolonged exposure to µG. We evaluated the transcriptomic changes induced by µG on board the International Space Station (ISS) in differentiating huMPCs isolated from Vastus lateralis muscle biopsies of a pre-flight astronaut and an age- and sex-matched volunteer, in comparison with the same cells cultured on the ground in standard gravity (1×g) conditions. We found that huMPCs differentiated under real µG conditions showed: (i) upregulation of genes related to cell adhesion, plasma membrane components, and ion transport; (ii) strong downregulation of genes related to the muscle contraction machinery and sarcomere organization; and (iii) downregulation of muscle-specific microRNAs (myomiRs). Moreover, we had the unique opportunity to analyze huMPCs and skeletal muscle tissue of the same astronaut before and 30 h after a long-duration space flight on board the ISS. Prolonged exposure to real µG strongly affected the biology and functionality of the astronaut’s satellite cells, which showed a dramatic reduction of responsiveness to activating stimuli and proliferation rate, morphological changes, and almost inability to fuse into myotubes. RNA-Seq analysis of post- vs. pre-flight muscle tissue showed that genes involved in muscle structure and remodeling are promptly activated after landing following a long-duration space mission. Conversely, genes involved in the myelination process or synapse and neuromuscular junction organization appeared downregulated. Although we have investigated only one astronaut, these results point to a prompt readaptation of the skeletal muscle mechanical components to the normal gravitational loading, but the inability to rapidly recover the physiological muscle myelination/innervation pattern after landing from a long-duration space flight. Together with the persistent functional deficit observed in the astronaut’s satellite cells after prolonged exposure to real µG, these results lead us to hypothesize that a condition of inefficient regeneration is likely to occur in the muscles of post-flight astronauts following damage.

LIDAL (Light Ion Detector for ALTEA, Anomalous Long-Term Effects on Astronauts) is a radiation detector designed to measure the flux, the energy spectra and, for the first time, the time-of-flight of ions in a space habitat. It features a combination of striped silicon sensors for the measurement of deposited energy (using the ALTEA device, which operated from 2006 to 2012 in the International Space Station) and fast scintillators for the time-of-flight measurement. LIDAL was tested and calibrated using the proton beam line at TIFPA (Trento Institute for Fundamental Physics Application) and the carbon beam line at CNAO (National Center for Oncology Hadron-therapy) in 2019. The performance of the time-of-flight system featured a time resolution (sigma) less than 100 ps. Here, we describe the detector and the results of these tests, providing ground calibration curves along with the methodology established for processing the detector’s data. LIDAL was uploaded in the International Space Station in November 2019 and it has been operative in the Columbus module since January 2020.