Regulation of the Response of Caenorhabditis elegans to Simulated Microgravity by p38 Mitogen-Activated Protein Kinase Signaling

Reports that aging slows down in space prompted this investigation of anti-aging effects in humans by analyzing astronauts’ heart rate variability (HRV). Ambulatory 48-hour electrocardiograms from 7 astronauts (42.1 ± 6.8 years; 6 men) 20.6 ± 2.7 days (ISS01) and 138.6 ± 21.8 days (ISS02) after launch were divided into 24-hour spans of relative lower or higher magnetic disturbance, based on geomagnetic measures in Tromso, Norway. Magnetic disturbances were significantly higher on disturbed than on quiet days (ISS01: 72.01 ± 33.82 versus 33.96 ± 17.90 nT, P = 0.0307; ISS02: 71.06 ± 51.52 versus 32.53 ± 27.27 nT, P = 0.0308). SDNNIDX was increased on disturbed days (by 5.5% during ISS01, P = 0.0110), as were other HRV indices during ISS02 (SDANN, 12.5%, P = 0.0243; Triangular Index, 8.4%, P = 0.0469; and TF-component, 17.2%, P = 0.0054), suggesting the action of an anti-aging or longevity effect. The effect on TF was stronger during light (12:00–17:00) than during darkness (0:00–05:00) (P = 0.0268). The brain default mode network (DMN) was activated, gauged by increases in the LF-band (9.7%, P = 0.0730) and MF1-band (9.9%, P = 0.0281). Magnetic changes in the magnetosphere can affect and enhance HRV indices in space, involving an anti-aging or longevity effect, probably in association with the brain DMN, in a light-dependent manner and/or with help from the circadian clock.

Section: Discussionmentioning

confidence: 99%

Anti-aging effects of long-term space missions, estimated by heart rate variability

Otsuka

Cornélissen

Kubo

et al. 2019

“…That is, during the control of toxicity of simulated microgravity, we also raised an intestinal signaling cascade of SKN-1a-GST-4/GST-5/GST-7. Our previous study has suggested that the activation of PMK-1/p38 MAPK-SKN-1 mediated a protective response to simulated microgravity 20 . In this study, we further found that the decrease in let-7 could further enhance the p38 MAPK signaling pathway-mediated protective response to simulated microgravity by targeting SKN-1 s. Our results in this study provided an important molecular basis for our understanding the epigenetic control of response to simulated microgravity in organisms.…”

Section: Discussionmentioning

confidence: 94%

“…Recently, the toxicity of simulated microgravity could also be detected in nematodes 17 – 19 . Simulated microgravity could induce production of intestinal reactive oxygen species (ROS) and inhibition in locomotion behavior in nematodes 20 . Meanwhile, insulin, p38 mitogen-activated protein kinase (MAPK), and Wnt signaling pathways were required for toxicity induction in simulated microgravity treated nematodes 19 – 21 .…”

Section: Introductionmentioning

confidence: 99%

microRNAs involved in the control of toxicity on locomotion behavior induced by simulated microgravity stress in Caenorhabditis elegans

Sun

et al. 2020

Self Cite

microRNAs (miRNAs) post-transcriptionally regulate the expression of targeted genes. We here systematically identify miRNAs in response to simulated microgravity based on both expressions and functional analysis in Caenorhabditis elegans. After simulated microgravity treatment, we observed that 19 miRNAs (16 down-regulated and 3 up-regulated) were dysregulated. Among these dysregulated miRNAs, let-7, mir-54, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 were required for the toxicity induction of simulated microgravity in suppressing locomotion behavior. In nematodes, alteration in expressions of let-7, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 mediated a protective response to simulated microgravity, whereas alteration in mir-54 expression mediated the toxicity induction of simulated microgravity. Moreover, among these candidate miRNAs, let-7 regulated the toxicity of simulated microgravity by targeting and suppressing SKN-1/Nrf protein. In the intestine, a signaling cascade of SKN-1/Nrf-GST-4/GST-5/GST-7 required for the control of oxidative stress was identified to act downstream of let-7 to regulate the toxicity of simulated microgravity. Our data demonstrated the crucial function of miRNAs in regulating the toxicity of simulated microgravity stress in organisms. Moreover, our results further provided an important molecular basis for epigenetic control of toxicity of simulated microgravity.

“…elegans Experiment in Space” (ICE-First) experiments as an example, it has been observed that microgravity could potentially at least cause the toxicity on early embryogenesis, muscle development, germline development, locomotion behavior, and reproduction in nematodes 17–23 . The toxicity of simulated microgravity on nematodes could be further assessed more recently 24–27 . The observed toxicity induced by simulated microgravity was under the control of insulin and p38 mitogen-activated protein kinase (MAPK) signaling pathways in nematodes 24,26 .…”

Section: Introductionmentioning

confidence: 99%

“…The toxicity of simulated microgravity on nematodes could be further assessed more recently 24–27 . The observed toxicity induced by simulated microgravity was under the control of insulin and p38 mitogen-activated protein kinase (MAPK) signaling pathways in nematodes 24,26 .…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Unfolded Protein Response to Microgravity Stress in Nematode Caenorhabditis elegans

Liu

et al. 2019

Self Cite

Caenorhabditis elegans is useful for assessing biological effects of spaceflight and simulated microgravity. The molecular response of organisms to simulated microgravity is still largely unclear. Mitochondrial unfolded protein response (mt UPR) mediates a protective response against toxicity from environmental exposure in nematodes. Using HSP-6 and HSP-60 as markers of mt UPR, we observed a significant activation of mt UPR in simulated microgravity exposed nematodes. The increase in HSP-6 and HSP-60 expression mediated a protective response against toxicity of simulated microgravity. In simulated microgravity treated nematodes, mitochondria-localized ATP-binding cassette protein HAF-1 and homeodomain-containing transcriptional factor DVE-1 regulated the mt UPR activation. In the intestine, a signaling cascade of HAF-1/DVE-1-HSP-6/60 was required for control of toxicity of simulated microgravity. Therefore, our data suggested the important role of mt UPR activation against the toxicity of simulated microgravity in organisms.