Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

Abstract

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and ground-based models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

Oxidative Stress and Space Biology: An Organ-Based Approach

“…These responses tied to excess ROS/RNS, (NO) and inflammation are implicated both in diseases of aging, like osteoporosis and atherosclerosis, and pursuant to insults such as radiation exposure as seen in spaceflight. ROS can directly facilitate bone osteoclastogenesis, leading to resorption and bone loss during aging and estrogen deficiency may be partly attributed to OSaD mechanisms, and thus portends to link the complex phenomena of bone and muscle loss, vascular deconditioning, and immune functions together in an intricate syndrome [ 13 ].…”

“…Tahimic and Globus [ 13 ] note the increase in pro-inflammatory conditions, which involve immune function and general metabolism. These increases are in part the result of physiological changes enumerated in the sections above [ 11 , 12 , 13 , 14 ]. Blaber et al goes further to define the system biology of space flight in a study performed on mice sent to space for only 13.5 days aboard the Space Shuttle Atlantis.…”

“…As we turn to countermeasures we see that in many of the previous manuscripts and reviews cited potential mitigating agents are either physiologically endemic, naturally occurring, or pharmacologic [ 12 , 13 , 14 , 15 , 16 , 17 ]. In this review Endesfelder et al details the mechanisms of caffeine a potent free radical scavenger and adenosine receptor antagonist.…”

“…Space flight adaptation syndromes are a product of the environmental conditions and the synergistic reaction of the systemic human physiology, which together combine to produce a combinatorial syndrome that must be resolved in order to safely inhabit and explore space, especially for extended periods [ 3 , 4 , 5 , 6 ]. This paper documents an exciting glimpse of current pertinent scientific literature sustaining the involvement of oxidative stress and damage (OSaD) [ 7 , 8 ] as a significant contributing factor in the following areas of Earth-based and space flight-related dysregulation of: (1) bone loss [ 9 , 10 , 11 , 12 , 13 ]; (2) cardiovascular function [ 14 ]; (3) immune insufficiency and metabolism [ 15 , 16 , 17 ]; (4) neurological impairment [ 18 ]; and (5) potential countermeasure implementation [ 18 , 19 ]. The cited literature illuminates the environmental challenges of spaceflight encompassing reduced gravity, radiation, varying atmospheric conditions, such as hyperoxia and hypoxia experienced during extravehicular and intravehicular activity (EVA/IVA), and evidence of synergistic effects that portend substantial consequences for long duration/exploration class missions.…”

Transcriptional Homeostasis of Oxidative Stress-Related Pathways in Altered Gravity

“…ROS/RNS are serving as signals in many diverse circumstances and as a central part of cellular homeostasis [ 2 ]. Oxidative stress and damage has been identified as a contributing factor to spaceflight-related dysregulation of the bone [ 8 , 9 , 10 , 11 , 12 ], the cardiovascular system [ 13 ], the immune system, and metabolism [ 14 , 15 ]. Thus, normalizing the redox homeostasis could mitigate a portion of the adverse phenomena seen in spaceflight, increasing the level of health and safety during exploration class missions [ 16 ].…”