Physiological System Dysregulation in Gene Expression Correlates Negatively with Age

Abstract

We attempted to identify gene expression systems that dysregulate with age in human peripheral blood samples across five public datasets. Dysregulation of gene ontology (GO)-defined systems was measured using the Mahalanobis distance (DM), a measure of multivariant aberrance. We expected many weak positive DM-age correlations, indicating loss of homeostatic control. Out of the 5180 GO terms tested, we found 230 systems that replicated in at least three datasets. Surprisingly, all 230 systems showed negative DM-age correlations, in contrast to findings with clinical biomarkers. These systems were mostly metabolic functions related to small molecules and nitrogen compounds, transport functions, biosynthetic processes and response to stress functions. These results suggest a loss of responsiveness in these gene expression systems during the aging process, and contrast to some previous literature showing increased gene expression heterogeneity with age.