Sex-dimorphic and age-dependent organization of 24-hour gene expression rhythms in humans

Abstract

The circadian clock modulates human physiology. However, the organization of tissue-specific gene expression rhythms and how these depend on age and sex is not defined in humans. We combined data from the Genotype-Tissue Expression (GTEx) project with an algorithm that assigns circadian phases to 914 donors, by integrating temporal information from multiple tissues in each individual, to identify messenger RNA (mRNA) rhythms in 46 tissues. Clock transcripts showed conserved timing relationships and tight synchrony across the body. mRNA rhythms varied in breadth, covering global and tissue-specific functions, including metabolic pathways and systemic responses. The clock structure was conserved across sexes and age groups. However, overall gene expression rhythms were highly sex-dimorphic and more sustained in females. Rhythmic programs generally dampened with age across the body.

Tracking human circadian gene expression

Rhythmic circadian changes in gene expression have been well documented in model organisms, but data are limited from primates and particularly humans. Talamanca et al . developed an algorithm that allowed them to assign a circadian phase to each individual in a set of about 900 human donors. This approach allowed them to detect circadian changes in gene expression in samples from 46 tissues. Women showed higher rhythmicity of transcripts, especially in liver and the adrenal gland. The results also confirmed that rhythmicity was generally damped in older individuals. —LBR

Abstract

Daily rhythms of gene expression in humans vary according to sex and age.