Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space ...travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.
An international group of spaceflight researchers detail how spaceflight affects human biology from the molecular to physiological level and identify key challenges for making space exploration compatible with human health.
Bone marrow adipose tissue (BMAT) is hypothesized to serve as an expandable/contractible fat depot which functions, in part, to minimize energy requirements for sustaining optimal hematopoiesis. We ...investigated whether BMAT is required for immune reconstitution following injury. Male wild type (WBB6F1, WT) and BMAT-deficient WBB6F1/J-
/J (
) mice were lethally irradiated. Irradiation was followed by adoptive transfer of 1000 purified WT hematopoietic stem cells (HSCs). The extent of immune reconstitution in blood, bone marrow, and lymph nodes in the irradiated mice was determined using HSCs from green fluorescent protein (GFP)-expressing mice. We also evaluated skeletal response to treatment. Detection of GFP-positive B and T cells in peripheral blood at 4 and 9 weeks following adoptive transfer and in bone marrow and lymph nodes following necropsy revealed excellent immune reconstitution in both WT and BMAT-deficient mice. Adipocytes were numerous in the distal femur of WT mice but absent or rare in
mice. Bone parameters, including length, mass, density, bone volume, microarchitecture, and turnover balance, exhibited few differences between WT and BMAT-deficient mice. The minimal differences suggest that BMAT is not required for reconstitution of the immune system following lethal radiation and is not a major contributor to the skeletal phenotypes of kit signaling-deficient mice.
This study investigated the effects of a 14-day spaceflight on bone mass, density and microarchitecture in weight bearing (femur and humerus) and non-weight bearing (2(nd) lumbar vertebra and ...calvarium) bones in the context of ovarian hormone insufficiency. 12-week-old Fisher 344 rats were ovariectomized 2 weeks before flight and randomized into one of three groups: 1) baseline (n = 6), 2) ground control (n = 12) or 3) spaceflight (n = 12). Additional ground-based ovary-intact rats provided age-matched reference values at baseline (n = 8) and landing (n = 10). Ovariectomy resulted in bone- and bone compartment-specific deficits in cancellous bone volume fraction. Spaceflight resulted in lower cortical bone accrual in the femur but had no effect on cortical bone in the humerus or calvarium. Cancellous bone volume fraction was lower in flight animals compared to ground control animals in lumbar vertebra and distal femur metaphysis and epiphysis; significant differences were not detected in the distal humerus. Bone loss (compared to baseline controls) in the femur metaphysis was associated with lower trabecular number, whereas trabecular thickness and number were lower in the epiphysis. In summary, the effect of spaceflight on bone microarchitecture in ovariectomized rats was bone-and bone compartment-specific but not strictly related to weight bearing.
Based on body weight, morbidly obese leptin-deficient ob/ob mice have less bone than expected, suggesting that leptin plays a role in the skeletal response to weight bearing. To evaluate this ...possibility, we compared the skeletal response of wild type (WT) and ob/ob mice to hindlimb unloading (HU). Mice were individually housed at 32 °C (thermoneutral) from 4 weeks of age (rapidly growing) to 16 weeks of age (approaching skeletal maturity). Mice were then randomized into one of 4 groups (n = 10/group): (1) WT control, (2) WT HU, (3) ob/ob control, and (4) ob/ob HU and the results analyzed by 2-way ANOVA. ob/ob mice pair-fed to WT mice had normal cancellous bone volume fraction (BV/TV) in distal femur, lower femur length and total bone area, mineral content (BMC) and density (BMD), and higher cancellous bone volume fraction in lumbar vertebra (LV). HU resulted in lower BMC and BMD in total femur, and lower BV/TV in distal femur and LV in both genotypes. Cancellous bone loss in femur in both genotypes was associated with increases in osteoclast-lined bone perimeter. In summary, leptin deficiency did not attenuate HU-induced osteopenia in male mice, suggesting that leptin is not required for bone loss induced by unweighting.
Bone marrow adipose tissue (MAT) is negatively associated with bone mass. Since osteoblasts and adipocytes are derived from the same precursor cells, adipocyte differentiation may occur at the ...expense of osteoblast differentiation. We used MAT-deficient Kit
(MAT-) mice to determine if absence of MAT reduced bone loss in hindlimb-unloaded (HU) mice. Male MAT- and wild-type (WT) mice were randomly assigned to a baseline, control or HU group (n = 10 mice/group) within each genotype and HU groups unloaded for 2 weeks. Femurs were evaluated using micro-computed tomography, histomorphometry and targeted gene profiling. MAT- mice had a greater reduction in bone volume fraction after HU than did WT mice. HU MAT- mice had elevated cancellous bone formation and resorption compared to other treatment groups as well as a unique profile of differentially expressed genes. Adoptive transfer of WT bone marrow-derived hematopoietic stem cells reconstituted c-kit but not MAT in Kit
mice. The MAT- WT → Kit
mice lost cancellous bone following 2 weeks of HU. In summary, results from this study suggest that MAT deficiency was not protective, and was associated with exaggerated disuse-induced cancellous bone loss.
There is often a reciprocal relationship between bone marrow adipocytes and osteoblasts, suggesting that marrow adipose tissue (MAT) antagonizes osteoblast differentiation. MAT is increased in ...rodents during spaceflight but a causal relationship between MAT and bone loss remains unclear. In the present study, we evaluated the effects of a 14-day spaceflight on bone mass, bone resorption, bone formation, and MAT in lumbar vertebrae of ovariectomized (OVX) rats. Twelve-week-old OVX Fischer 344 rats were randomly assigned to a ground control or flight group. Following flight, histological sections of the second lumbar vertebrae (
=11/group) were stained using a technique that allowed simultaneous quantification of cells and preflight fluorochrome label. Compared with ground controls, rats flown in space had 32% lower cancellous bone area and 306% higher MAT. The increased adiposity was due to an increase in adipocyte number (224%) and size (26%). Mineral apposition rate and osteoblast turnover were unchanged during spaceflight. In contrast, resorption of a preflight fluorochrome and osteoclast-lined bone perimeter were increased (16% and 229%, respectively). The present findings indicate that cancellous bone loss in rat lumbar vertebrae during spaceflight is accompanied by increased bone resorption and MAT but no change in bone formation. These findings do not support the hypothesis that increased MAT during spaceflight reduces osteoblast activity or lifespan. However, in the context of ovarian hormone deficiency, bone formation during spaceflight was insufficient to balance increased resorption, indicating defective coupling. The results are therefore consistent with the hypothesis that during spaceflight mesenchymal stem cells are diverted to adipocytes at the expense of forming osteoblasts.
The impact of 3D groundwater dynamics as part of the hydrologic cycle is rarely considered in regional climate simulation experiments. However, there exists a spatial and temporal connection between ...groundwater and soil moisture near the land surface, which can influence the land surface‐atmosphere feedbacks during heat waves. This study assesses the sensitivity of bedrock‐to‐atmosphere simulations to groundwater representations at the continental scale during the European heat wave 2003 using an integrated fully coupled soil‐vegetation‐atmosphere model. The analysis is based on the comparison of two groundwater configurations: (1) 3D physics‐based variably saturated groundwater dynamics and (2) a 1D free drainage (FD) approach. Furthermore, two different subsurface hydrofacies distributions (HFD) account for the uncertainty of the subsurface hydraulic characteristics, and ensemble simulations address the uncertainty arising from different surface‐subsurface initial conditions. The results show that the groundwater representation significantly impacts land surface‐atmosphere processes. Differences between the two groundwater configurations follow subsurface patterns, and the largest differences are observed for shallow water table depths. While the physics‐based setup is less sensitive to the HFD, the parameterized FD simulations are highly sensitive to the hydraulic characteristics of the subsurface. An analysis of variance shows that both, the groundwater configuration and the HFD, induce variability across all compartments with decreasing impact from the subsurface to the atmosphere, while the initial condition has only a minor impact.
Key Points
Continental modeling of the water and energy cycle from groundwater into the atmosphere
Impact study of groundwater dynamics and parameterizations on atmospheric processes
Land surface and atmospheric variability is induced by the groundwater configuration
Social scientists need practical methods for harnessing large, publicly available datasets that inform the social context of aging. We describe our development of a semi-automated text coding method ...and use a content analysis of Alzheimer's disease (AD) and dementia portrayal on Twitter to demonstrate its use. The approach improves feasibility of examining large publicly available datasets.
Machine learning techniques modeled stigmatization expressed in 31,150 AD-related tweets collected via Twitter's search API based on 9 AD-related keywords. Two researchers manually coded 311 random tweets on 6 dimensions. This input from 1% of the dataset was used to train a classifier against the tweet text and code the remaining 99% of the dataset.
Our automated process identified that 21.13% of the AD-related tweets used AD-related keywords to perpetuate public stigma, which could impact stereotypes and negative expectations for individuals with the disease and increase "excess disability".
This technique could be applied to questions in social gerontology related to how social media outlets reflect and shape attitudes bearing on other developmental outcomes. Recommendations for the collection and analysis of large Twitter datasets are discussed.
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