The NASA Twins Study: The Effect of One Year in Space on Long-Chain Fatty Acid Desaturases and Elongases.

IF 2 4区 医学 Q3 GENETICS & HEREDITY
Lifestyle Genomics Pub Date : 2020-01-01 Epub Date: 2020-05-06 DOI:10.1159/000506769
Michael A Schmidt, Cem Meydan, Caleb M Schmidt, Ebrahim Afshinnekoo, Christopher E Mason
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引用次数: 0

Abstract

Background: At present, there is no clear understanding of the effect of long-duration spaceflight on the major enzymes that govern the metabolism of omega-6 and omega-3 fatty acids. To address this gap in knowledge, we used data from the NASA Twins Study, which includes a multiscale omics investigation of the changes that occurred during a year-long (340 days) human spaceflight. Embedded within the NASA Twins data are specific analytes associated with fatty acid metabolism.

Objectives: To examine the long-chain fatty acid desaturases and elongases in a single human during 1 year in space.

Method: One male twin was on board the International Space Station (ISS) for 1 year, while his monozygotic twin served as a genetically matched ground control. Longitudinal assessments included the genome, epige-nome, transcriptome, proteome, metabolome, microbiome, and immunome during the mission, as well as 6 months before and after. The gene-specific fatty acid desaturase and elongase transcriptome data (FADS1, FADS2, ELOVL2, and ELOVL5) were extracted from untargeted RNA-seq measurements derived from white blood cell fractions.

Results: Most data from the elongases and desaturases exhibited relatively similar expression profiles (R2 >0.6) over time for the CD8, CD19, and lymphocyte-depleted (LD) cell fractions, indicating overall conservation of function within and between the subjects. Both cell-type and temporal specificity was observed in some cases, and some differences were also apparent between the polyadenylated (polyA) fraction of processed RNAs versus the ribodepleted (ribo-) fraction. The flight subject showed a stronger enrichment of the fatty acid metabolic process pathway across almost all cell types (columns, CD4, CD8, CPT, and LD), most especially in the ribodepleted fraction of RNA, but also with the polyA+ fraction of RNA. Gene set enrichment analysis (GSEA) measures across three related fatty acid metabolism pathways showed a differential between the ground and the flight subject.

Conclusions: There appears to be no persistent alteration of desaturase and elongase gene expression associated with 1 year in space. However, these data provide evidence that cellular lipid metabolism can be responsive and dynamic to spaceflight, even though it appears cell-type and context specific, most notably in terms of the fraction of RNA measured and the collection protocols. These results also provide new evidence of mid-flight spikes in expression of selected genes, which may indicate transient responses to specific insults during spaceflight.

美国国家航空航天局双胞胎研究:太空一年对长链脂肪酸去饱和酶和伸长酶的影响。
背景:目前,人们还不清楚长期太空飞行对支配欧米伽-6 和欧米伽-3 脂肪酸代谢的主要酶的影响。为了填补这一知识空白,我们使用了美国宇航局双胞胎研究(NASA Twins Study)的数据,该研究包括对为期一年(340 天)的人类太空飞行期间发生的变化进行多尺度omics调查。NASA Twins 数据中包含了与脂肪酸代谢相关的特定分析物:目的:研究人类在太空飞行一年期间的长链脂肪酸去饱和酶和伸长酶:方法:一名男性双胞胎在国际空间站(ISS)上生活了一年,他的单卵双胞胎作为遗传匹配的地面对照。纵向评估包括任务期间以及任务前后 6 个月的基因组、外显子组、转录组、蛋白质组、代谢组、微生物组和免疫组。基因特异性脂肪酸去饱和酶和伸长酶转录组数据(FADS1、FADS2、ELOVL2 和 ELOVL5)是从白细胞分馏物的非靶向 RNA-seq 测量中提取的:在 CD8、CD19 和去淋巴细胞 (LD) 细胞分馏物中,伸长酶和去饱和酶的大多数数据都显示出相对相似的表达谱(R2 >0.6),表明受试者体内和受试者之间的功能总体保持不变。在某些情况下观察到了细胞类型和时间特异性,处理过的 RNA 中的多聚腺苷酸(polyA)部分与去核糖核酸(ribo)部分之间也存在一些明显的差异。飞行实验对象显示,脂肪酸代谢过程途径在几乎所有细胞类型(柱、CD4、CD8、CPT 和 LD)中都有较强的富集,尤其是在核糖核酸耗尽部分,但也包括核糖核酸的 polyA+ 部分。三个相关脂肪酸代谢途径的基因组富集分析(GSEA)结果显示,地面实验对象与飞行实验对象之间存在差异:结论:在太空飞行 1 年,去饱和酶和伸长酶基因表达似乎没有发生持续性改变。然而,这些数据提供了细胞脂质代谢对太空飞行具有反应性和动态性的证据,尽管这种反应性和动态性似乎与细胞类型和环境有关,特别是在所测量的 RNA 部分和收集方案方面。这些结果还提供了新的证据,证明选定基因的表达在飞行中期出现峰值,这可能表明在太空飞行期间对特定损伤的瞬时反应。
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来源期刊
Lifestyle Genomics
Lifestyle Genomics Agricultural and Biological Sciences-Food Science
CiteScore
4.00
自引率
7.70%
发文量
11
审稿时长
28 weeks
期刊介绍: Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.
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