DOI: 10.1101/519520Jan 13, 2019Paper

Genetic dysregulation of gene expression and splicing during a ten-year period of human aging

BioRxiv : the Preprint Server for Biology
Brunilda BalliuStephen B Montgomery


Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age. We performed RNA sequencing in whole-blood from the same individuals from the PIVUS study at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age; 93% of samples cluster with their own measurement at another age, and there is a strong correlation of genetic effects on expression between the two ages (median ρG = 0.96). Despite this, we identify 1,291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories of aging. Further, 7.8% and 9.6% of tested genes show a reduction in genetic associations with expression and alternative splicing in older age, with impacted genes enriched in DNA...Continue Reading

Related Concepts

Alternative Splicing
Cross-Sectional Studies
DNA Repair
Gene Expression
RNA Splicing
Sequence Determinations, RNA
Protein Expression

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