Spaceflight alters insulin and estrogen signaling pathways

Abstract

Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here we extend molecular work to energy metabolism and sex hormone signaling in mice and humans. We found spaceflight-induced changes in insulin and estrogen signaling in rodents and humans. Murine changes were most prominent in the liver, where we observed inhibition of insulin and estrogen receptor signaling with concomitant hepatic insulin resistance and steatosis. Based on the metabolic demand, metabolic pathways mediated by insulin and estrogen vary among muscles, specifically between the soleus and extensor digitorum longus. In humans, spaceflight induced changes in insulin and estrogen related genes and pathways. Pathway analysis demonstrated spaceflight-induced changes in insulin resistance, estrogen signaling, stress response, and viral infection. These data strongly suggest the need for further research on the metabolic and reproductive endocrinologic effects of space travel, if we are to become a successful interplanetary species

A second space age spanning omics, platforms and medicine across orbits

“…While these systemic stresses appear universal, individuals experience varying degrees of dysregulation, necessitating astronaut-specific precision medicine to ensure safe space travel for all. Data from I4 and JAXA missions reveal both universal changes (increased inflammation and mitochondrial stress), independent of sex and ethnicity, and sex-specific variations (insulin and estrogen changes in females) 4,8,33 . By aggregating these findings, we can annotate systemic changes and construct a molecular fingerprint for key alterations indicated that individualized astronaut healthcare is crucial.…”

“…Mitochondrial and immune function are interconnected, impacting insulin and estrogen signaling, and posing heightened health risks for the female reproductive system 50 . An integrated analysis of murine, JAXA cfRNA, and I4 scRNA-seq data revealed altered mRNA levels during and after spaceflight, affecting mitochondrial metabolic pathways, particularly lipid metabolism and oxidative stress 4 . These changes contribute to heightened health risks associated with reproductive hormone synthesis.…”

“…Notably, females appear to be less affected by spaceflightassociated neuro-ocular syndrome (SANS), yet more affected in other modalities, such as vascular responses and possible cancer risk 2 . However, comprehensive studies on cell-specific and genetic changes in both sexes only began in 2021, revealing differences crucial for mission planning [3][4][5] .…”

Astronaut omics and the impact of space on the human body at scale

“…This enzyme superfamily is believed to account for 75% of total drug metabolism 28 . Indeed, CYPs have recently been suggested to be altered in flight due to alterations in insulin and estrogen signaling 29 . Several CYP450 genes are highly polymorphic, producing enzyme variants that cause variability in drug-metabolizing effects between groups.…”

Spaceflight Induces Strength Decline in Caenorhabditis elegans

“…While still in its infancy [24][25][26], it seems clear that combining -omics data from space-flown model organisms, such as C. elegans, Drosophila, and rodents, with astronaut data can accelerate the discovery process, in part by compensating for the current rarity of human space -omics datasets [22,27]. For example, C. elegans, rodents, and humans all display alterations in insulin-linked gene expression in response to spaceflight [28]. Given the central role of insulin in human health and longevity on Earth [29], it is highly likely this system is equally important to maintain in space.…”