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Multi-omics analysis of aging liver in female nonhuman primates.

ABSTRACT: The goal of this study was to identify molecular changes associated with healthy aging in the livers of female baboons (n=35) by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. To integrate omics data, we performed unbiased weighted gene co-expression network analysis (WGCNA), and the results revealed 3 modules containing 3,149 genes and 33 proteins were positively correlated with age, and 2 modules containing 37 genes and 216 proteins were negatively correlated with age. Pathway enrichment analysis showed that unfolded protein response and endoplasmic reticulum stress were positively associated with age, whereas xenobiotic metabolism and melatonin and serotonin degradation pathways were negatively associated with age.

ORGANISM(S): Papio sp.

PROVIDER: GSE243092 | GEO | 2026/09/01

REPOSITORIES: GEO

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Project description:Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects’ demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03) with age (R2=-0.23), vascular stiffness (R2=-0.24), and central aortic pressure (R2=-0.19) and positively correlated with body mass index (R2=0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients’ samples, which was reflected in reduced dispersion of their nodes’ degrees of connectivity, suggesting a more primitive character of the patients’ CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network. Furthermore, the coordinated gene expression in these modules can be linked to cardiovascular risk factors and subclinical cardiovascular disease; thus, this measure may be useful for their diagnosis and prognosis. PBMCs were isolated from 26 healthy subjects and 20 hypertensive patients by density gradient centrifugation. Total RNA was extracted from ~ 10^6 cells, reverse transcription was done using 150 ng RNA, and the real-time PCR was done in duplicate for each sample.

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Multi-omics analysis of aging liver in female nonhuman primates.

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