Age-associated increases in inter-individual gene expression variability across human tissues

Authors

Bartz, J., Rivera, P., Niedernhofer, L. J., Zhang, L., Dong, X.

Abstract

Aging involves progressive physiological decline, yet the underlying transcriptomic patterns remain poorly understood. Although differentially expressed genes (DEGs) have been the primary focus of previous studies, here we investigate differentially variable genes (DVGs) using a novel Gene Stability Score (GSS). In 30 tissue types from nearly 1,000 individuals in the Genotype-Tissue Expression (GTEx) project, age- and sex-related DVGs account for approximately 15% of overall expression variability between samples of the same tissue, with age-related DVGs specifically contributing 7.7%. We further show that DEGs and DVGs affect distinct biological pathways, and that inter-individual instability is significantly correlated with cell-to-cell transcriptional noise. Moreover, gene regulatory network analysis reveals that this variability is not random but is shaped by local network architecture. Finally, we identify robust reference genes, including TBP, PUM1, and TMEM199, for RT-qPCR experiments in studying age-related gene expression changes in humans. Together, our findings suggest that aging involves both coordinated transcriptional programs and increased stochasticity across individuals and cells.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 17 Apr 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.