Hypothetical role of hypoxia-inducible factor-1 in adaptations to microgravity

Maintaining health in microgravity and overcoming environmental hazards such as cosmic radiation are essential for long-term space flight. Recent studies have focused on the involvement of hypoxia-inducible factor (HIF)-1 in altered gravity using cell-based or in vivo mouse model systems. HIF-1alpha and its target downstream gene expression are differentially expressed in hypergravity and microgravity. Nevertheless, underlying molecular mechanism of HIF-1alpha involvement is still unclear. Herein, we analyzed the 2019 Science paper by Garrett-Bakelman and coauthors in which NASA performed multidimensional analyses of long-term human spaceflight in identical twin astronauts. Correlations were found between the expression of HIF-1alpha related cytokines and prolonged space flight. We hypothesize that HIF-1alpha is a molecular target for the development of therapeutics to prevent the detrimental effects of microgravity and cosmic radiation on astronauts during long-term space flight.

Mantener la salud en microgravedad y superar los peligros ambientales como la radiación cósmica son esenciales para los vuelos espaciales a largo plazo. Estudios recientes se han centrado en la participación del factor inducible por hipoxia (HIF) -1 en la gravedad alterada utilizando sistemas de modelos de ratones basados en células o in vivo. HIF-1alpha y su expresión génica secuencial objetivo se expresan diferencialmente en hipergravedad y microgravedad. Sin embargo, el mecanismo molecular subyacente de la participación de HIF-1alpha aún no está claro. Aquí, analizamos el artículo de Ciencia de 2019 de Garrett-Bakelman y coautores en el que la NASA realizó análisis multidimensionales de vuelos espaciales humanos a largo plazo en astronautas gemelos idénticos. Se encontraron correlaciones entre la expresión de citoquinas relacionadas con HIF-1alpha y el vuelo espacial prolongado. Presumimos que HIF-1alpha es un objetivo molecular para el desarrollo de terapias para prevenir los efectos perjudiciales de la microgravedad y la radiación cósmica en los astronautas durante los vuelos espaciales a largo plazo.

Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or without Artificial Gravity.

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions.Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis.Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m2): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA.Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR (P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group (P < 0.05).Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients.

Efectos fisiológicos en un ambiente de microgravedad / Physiological effects in an environment of microgravity

Resumen En el siglo veinte, el estudio del universo y el desarrollo de los vuelos espaciales fueron posibles gracias al avance tecnológico de naves de propulsión por diferentes tipos de cohetes. Muchos sistemas biológicos se afectan en los vuelos espaciales y se ha demostrado que en un ambiente de microgravedad se altera de manera significativa la función musculoesquelética, neurosensitiva, endócrina, renal, respiratoria y cardiovascular, además del riesgo de lesión debido a la exposición a diferentes tipos de radiación, eventos que comprometen la salud y rendimiento de los astronautas. Por lo anterior es fundamental mantener la salud y acondicionamiento físico de los astronautas durante el vuelo espacial para facilitar y acelerar su recuperación al llegar a la tierra.

Abstract Until the twentieth century, study about the universe and speculation about the nature of spaceflight were no closely related to the technical developments that led to rocket propulsión. Many biological systems are adversely affected by space flight and It has been shown that exposure to microgravity can alter the musculoskeletal, neurosensory, endocrine, renal, respiratory and cardiovascular systems and the risk of injury due to radiation exposure resulting in deconditioning that may compromise astronauts health and performance. Maintainig health and fitness during space missions is critical for preserving performance during misión specific tasks and to optimize terrestrial recovery.