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Frailty in middle age is associated with race-specific changes to the transcriptome.

ABSTRACT: Frailty is an aging-associated syndrome resulting from diminished capacity to respond to stressors, disrupted homeostasis. It is a significant risk factor for disability and mortality. Although frailty is usually studied in old age, it is present in mid-life. Given the increases in mortality statistics among middle-aged Americans, understanding molecular drivers of frailty in a younger, diverse cohort may facilitate identifying pathways for early intervention. We analyzed frailty-associated, genome-wide transcriptional changes in middle-aged African Americans (AAs) and whites. Next generation RNA sequencing was completed using total RNA from peripheral blood mononuclear cells. We analyzed differential gene expression patterns and completed a parametric analysis of gene set enrichment (PAGE). Differential gene expression was validated using RT-qPCR. We identified 5,082 genes differentially expressed with frailty. Frailty altered gene expression patterns and biological pathways differently in AAs and whites, including inflammatory and immune response pathways. The validation study showed a significant two-way interaction between frailty, race, and expression of the cytokine IL1B and the transcription factor EGR1. The glucose transporter, SLC2A6, the neutrophil receptor, FCGR3B, and the accessory protein, C17orf56, were decreased with frailty. These results suggest that there may be demographic dependent, divergent biological pathways underlying frailty diagnosis in middle-aged adults.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129534 | GEO | 2019/08/21

REPOSITORIES: GEO

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Frailty in middle age is associated with race-specific changes to the transcriptome.

Project description:Frailty in middle age is associated with race-specific changes to the transcriptome.

| PRJNA531676 | ENA

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