Composition of the whole transcriptome in the human plasma: Cellular source and modification by aging

Plasma contains several bioactive molecules (RNA, DNA, proteins, lipids, and metabolites), which are well preserved in extracellular vesicles, that are involved in many types of cell-to-cell interactions, and are capable of modifying biological processes in recipient cells. To obtain information about the source of mRNA molecules present in the plasma, we analyzed the plasma extracellular RNA (exRNA) of healthy individuals using RNA-sequencing and compared it to that of the peripheral blood mononuclear cell (PBMCs) of the same individual. The resultant data indicates that large proportion of the transcripts in plasma are derived from cell types other than PBMCs. To assess aging-associated changes in the plasma exRNA composition, gene ontology enrichment analysis was performed, revealing a functional decline in biological processes as a result of aging. Additionally, plasma RNA levels were analyzed with differential expression analysis, revealing 10 transcripts with significant aging-associated changes. Thus, it seems that the plasma exRNA is not fully derived from the PBMCs. Instead, other cell types supply RNAs to constitute the plasma exRNA compartment. This was true in both the young and elderly individuals that were tested. Furthermore, the RNA content of the plasma showed significant changes due to aging, affecting important biological processes. Seven plasma samples from healthy nonagenarians, aged 94, all female. Seven plasma samples from healthy young laboratory personnel, aged 26 to 32 median age 28, all female. The samples were RNA sequenced. Gene expression was quantified and studied.

血浆含有多种生物活性分子（RNA、DNA、蛋白质、脂质及代谢物），这些分子可通过细胞外囊泡（extracellular vesicles）得到良好保存，并参与多种细胞间相互作用，能够调控受体细胞的生物学过程。为明确血浆中mRNA分子的来源，本研究对健康个体的血浆细胞外RNA（extracellular RNA, exRNA）开展RNA测序分析，并将其与同一受试者的外周血单核细胞（peripheral blood mononuclear cell, PBMCs）的RNA进行比对。分析结果显示，血浆中绝大多数转录本并非源自PBMCs，而是来自其他细胞类型。为探究血浆exRNA组成随衰老发生的变化，本研究进行了基因本体（Gene Ontology, GO）富集分析，结果显示衰老会导致机体生物学过程出现功能衰退。此外，通过差异表达分析对血浆RNA水平进行探究，共鉴定出10个与衰老显著相关的差异转录本。由此可见，血浆exRNA并非完全来自PBMCs，其他细胞类型也会贡献RNA以构成血浆exRNA池。这一结论在本次研究的年轻及老年受试者群体中均成立。此外，血浆RNA含量会随衰老发生显著变化，并对核心生物学过程产生影响。本研究共纳入7份来自健康九旬老人的血浆样本（受试者年龄均为94岁，且均为女性），以及7份来自健康年轻实验室工作人员的血浆样本（受试者年龄为26至32岁，中位年龄28岁，且均为女性）；所有样本均进行了RNA测序，并对基因表达水平进行了定量分析与研究。