Life in space, involving prolonged exposure to hypogravity, is on the brink of becoming a reality. In 2024, the International Space Exploration Coordination Group (ISECG), comprising 27 space agencies, published the Global Exploration Roadmap. This document outlines a unified vision for long-term human and robotic exploration of the solar system.

According to the roadmap, human missions to the Moon are planned for 2027 under the Artemis III mission, while missions to Mars are targeted for 2035. NASA’s current focus is on the Artemis programme, which aims to lay the groundwork for future human exploration of Mars.

The prospect of extended human exposure to hypogravity presents significant challenges to astronauts’ health and performance in such a hostile environment. This workshop will cover the effects of actual and simulated spaceflight on the human body, with a particular focus on the neuromuscular and musculoskeletal systems, oxidative metabolism and mitochondrial function as well as nutrition, motor control, and Lunar locomotion. It will also address the impact of cosmic radiation on biological tissues, the effects of countermeasures, and review methods for simulating hypogravity on Earth.

A team of eight leading international experts in Life Sciences will present cutting-edge insights into these physiological challenges. They will highlight the major obstacles astronauts face during prolonged exposure to space environments, with the ultimate goal of enabling humans to thrive in these extreme conditions.

Date: Tuesday, 1 July
Time: 08:45-11:45
Session room: Tempio 1

Programme Agenda

Speaker

Prof Uros Marusic
Laboratory for Kinesiological Research
Science and Research Centre
Koper, Slovenia

Brain in Space: How Microgravity Reshapes Neural Control of Movement

Prof Marco Narici
Department of Biomedical Sciences
University of Padova
Padova, Italy

Neuromuscular impairment in simulated hypogravity

Prof Roberto Bottinelli
Department of Molecular Medicine
University of Pavia
Pavia, Italy

Mononuclear resident cells and skeletal muscle homeostasis in disuse: an overview.

Prof Bruno Grassi
Department of Medicine
University of Udine
Udine, Italy

Oxidative metabolism and mitochondrial function in simulated and actual spaceflight

Bert Blaauw
Department of Biomedical Sciences
University of Padova
Padova, Italy

Hibernation as countermeasure for spaceflight muscle athrophy?

Jonas Böcker
Institute of Aerospace Medicine
German Aerospace Centre
Cologne, Germany

Bone in Space: what are we going to do about it?

Prof Gianni Biolo
Department of Medical Sciences
University of Trieste
Trieste, Italy

A Multimodal Intervention to Prevent Muscle Atrophy, Insulin Resistance and Functional Decline During Experimental Bed Rest in Elderly Individuals

Prof Alberto Minetti
Locomotion Physiomechanics Laboratory
Department of Pathophysiology and Transplantation
University of Milan
Milan, Italy

Eight gaits from legged locomotion repertoire on Earth to be reliably adopted on the Moon

Prof Rado Pišot
Institute for Kinesiology Research
Science and Research Centre
Koper, Slovenia

Bedrest: A Ground-Based Model for Simulating Microgravity

Ad memoriam:

Prof Jörn Rittweger
Institute of Aerospace Medicine
German Aerospace Centre
Cologne, Germany

Prof Marco Narici
Department of Biomedical Sciences
University of Padova
Padova, Italy

Neuromuscular impairment in simulated hypogravity

Marco V. Narici^1,2, Evgeniia Motanova¹, Fabio Sarto¹, Giovanni Martino¹, Ornella Caputo¹, Martino Franchi¹, Uroš Marúsič², Giuseppe De Vito¹, Bostjan Siminič², Bruno Grassi³, Gianni Biolo⁴ and Rado Pišot²

¹Department of Biomedical Sciences, University of Padua, Italy;
²Science and Research Centre Koper, Slovenia;
³Department of Medicine, University of Udine, Udine, Italy;
⁴Department of Medical Sciences, University of Trieste, Italy

Chronic exposure to actual and simulated spaceflight profoundly affects the structural and functional integrity of the neuromuscular system1. Studies have shown that even short periods of unloading in simulated hypogravity can lead to loss of muscle mass, strength, as well as gene expression1, which are associated with significant neuromuscular alterations.

After just 3 days of unloading by dry-immersion, Demangel et al.2 reported significant muscle atrophy and force loss of the knee extensors associated by muscle fibre denervation.

Within ten days, signs of neuromuscular junction (NMJ) instability, altered NMJ morphology, extensive acetylcholine receptor remodelling, denervation, and axonal damage are observed3, 4. These changes result in altered motor unit recruitment threshold, reduced firing frequency, decreased conduction velocity, reduced neuromodulatory contribution by monoaminergic neurotransmitters5 (fundamental for setting the gain of spinal motor neurons excitability), and impaired NMJ transmission7, collectively leading to a loss of muscle strength and power exceeding what predicted by muscle atrophy alone5,6,7.

Recent evidence suggests that mitochondrial dysfunction, both near the NMJ in skeletal muscle fibers and within motor neuron terminals, may be a key factor responsible for NMJ instability and muscle denervation. Motanova et al.8, in a 10-day bed rest study, demonstrated that NMJ remodelling, characterised by decreased overlap between presynaptic and postsynaptic NMJ terminals, likely impairs NMJ transmission and signal propagation. Our data suggest that these changes are driven by oxidative stress, increased mitochondrial fission, and decreased mitochondrial volume density, ultimately triggering denervation and contributing to the loss of muscle strength and power observed in simulated hypogravity.

References:

• Pišot R. et al. (2016). J Appl Physiol., 120(8):922-9.
• Cam, F. et al. (2007). Journal of Applied Physiology, 102(6), 2315–2321.
• Demangel, R. et al. (2017). J Physiol, 595(13), 4301–4315.
• Monti, E. et al. (2021). Journal of Physiology, 599(12), 3037-3061
• Martino G. et al. (2024). Med Sci Sports Exerc., 56(9):1830-1839.
• Marusic U. et al. (2021). J Appl Physiol., 131(1):194-206.
• Sarto, F. et al. (2022). Journal of Physiology, 600(21), 4731-4751.

Motanova et al. (2025). J Physiol (In press)

Prof Uros Marusic
Laboratory for Kinesiological Research
Science and Research Centre
Koper, Slovenia

Brain in Space: How Microgravity Reshapes Neural Control of Movement

Uros Marusic¹, Bostjan Simunič¹, Gianni Biolo², Carlo Reggiani^1,4, Bruno Grassi³, Marco Narici^1,4, Rado Pišot¹

¹Institute for Kinesiology Research, Science and Research Centre Koper, Slovenia;
²Department of Medical Sciences, University of Trieste, Italy
³Department of Medicine, University of Udine¸ Italy
⁴Department of Biomedical Sciences, University of Padova, Padua, Italy

Exposure to weightlessness leads to significant structural and functional changes in the human brain, particularly affecting sensorimotor control. Spaceflight leads to headward fluid shifts, ventricular enlargement, cortical remodeling and altered brain positioning. These adaptations disrupt vestibular, proprioceptive and tactile inputs, leading to temporary impairments in sensorimotor integration upon return to Earth. Astronauts often suffer from balance problems, altered gait patterns and impaired movement coordination after flight. Ground-based bed rest studies effectively simulate these microgravity-induced changes, but their effects on the brain dynamics associated with locomotion have not yet been sufficiently explored.

To address this gap, we conducted a 10-day bed rest study in healthy older men (69 ± 3 years) using mobile brain/body imaging. Locomotor-related activity was assessed as participants walked for 2 minutes at their self-selected gait speed, with spatiotemporal gait parameters recorded using whole-body kinematics (Motion Shadow, USA) while brain dynamics were simultaneously monitored with a mobile 128-channel EEG (Cognionics, USA). We hypothesized that re-exposure to sensory input after bed rest would lead to increased theta synchronization in the anterior cingulate cortex (ACC) and posterior parietal cortex (PPC) due to prolonged immobilization. Gait-related spectral perturbations will be presented to elucidate possible neural mechanisms underlying altered locomotor capacity after bed rest and provide insights into spaceflight-induced neuromotor adaptations.

Prof Roberto Bottinelli
Department of Molecular Medicine
University of Pavia
Pavia, Italy

Mononuclear resident cells and skeletal muscle homeostasis in disuse: an overview.

Roberto Bottinelli¹, Maira Rossi^{1, 2}, Simone Porcelli¹, Cristiana Sazzi¹, Lorenza Brocca¹, Lorenzo Puri², Maria Antonietta Pellegrino¹

¹Department of Molecular Medicine University of Pavia, Italy;
²Development, Ageing and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA

So far, most studies aiming to clarify the mechanisms underlying muscle deterioration following disuse have understandably focused on muscle fibers and intracellular pathways controlling muscle mass, metabolism, and redox balance. However, a clear and comprehensive explanation of why loss of muscle mass and force occurs is still lacking. Recently, it has been understood that, although satellite cells are the stem cells which do repair and regenerate skeletal muscle fibers, other resident mononuclear cell populations (i.e., Fibro-Adipogenic Progenitors (FAPs), endothelial cells, immune cells, pericytes, tenocytes, glial cells, and Schwann cells) could play important roles not only in regeneration, but also in normal muscle homeostasis in conditions such as disuse and ageing (1). Among such cells, FAPs attracted most attention so far as a pivotal cell type that coordinates the activity of other muscle resident cell types, in response to homeostatic perturbations, via heterotypic interactions (5). While originally identified as interstitial muscle resident cells endowed with an inducible lineage bipotency, supporting either skeletal muscle regeneration or fibro-adipogenic degeneration (2, 4), subsequent studies have revealed a further functional heterogeneity. In particular, a growing amount of evidence is pointing to FAPs as mediators of muscle atrophy in response to denervation and ageing, possibly through interactions with neuromuscular junctions (NMJs) and NMJ-associated glial cells (3).

The potential role of FAPS cells and other mononuclear cell populations in normal muscle homeostasis and in disuse will be discussed.

References:

• mesenchymal-derived cells and immune cells in muscle homeostasis, regeneration and disease. Cell Death Dis 6: e1830, 2015. doi: 10.1038/cddis.2015.198
• Joe AW, Yi L, Natarajan A, Le Grand F, So L, Wang J, Rudnicki MA, and Rossi FM. Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat Cell Biol 12: 153-163, 2010. doi: 10.1038/ncb2015
• Nicoletti C, Wei X, Etxaniz U, D'Ercole C, Madaro L, Perera R, and Puri PL. Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF. iScience 26: 107114, 2023. doi: 10.1016/j.isci.2023.107114
• Uezumi A, Ikemoto-Uezumi M, Zhou H, Kurosawa T, Yoshimoto Y, Nakatani M, Hitachi K, Yamaguchi H, Wakatsuki S, Araki T, Morita M, Yamada H, Toyoda M, Kanazawa N, Nakazawa T, Hino J, Fukada SI, and Tsuchida K. Mesenchymal Bmp3b expression maintains skeletal muscle integrity and decreases in age-related sarcopenia. J Clin Invest 131, 2021. doi: 10.1172/JCI139617
• Wei X, Nicoletti C, and Puri PL. Fibro-Adipogenic Progenitors: Versatile keepers of skeletal muscle homeostasis, beyond the response to myotrauma. Semin Cell Dev Biol 119: 23-31, 2021. doi: 10.1016/j.semcdb.2021.07.013