Circadian gene expression varies according to sex and age

Daily rhythms of gene expression in humans vary according to sex and age, according to a new study using more than 900 human transcriptomes from the Genotype-tissue Expression (GTEx) project. The findings reveal a previously unknown diversity of sex- and age-specific differences in circadian gene expression, which could help explain the different incidences of some diseases in males and females, as well as during aging. The circadian clock modulates human physiology and synchronizes many aspects of our biology with daily environmental and societal cues. However, rhythmic circadian changes in gene expression aren’t well understood in humans, particularly how they relate to age and sex. To better understand the interactions between sexual dimorphism and the molecular circadian rhythms in humans, Lorenzo Talamanca and colleagues combined RNA sequencing data from 914 human donors with an algorithm that used temporal markers within tissues to detect and time-stamp each individual’s transcriptome with a circadian phase. The approach allowed the authors to view 24-hour gene expression rhythms across 46 human tissues. Talamanca et al. found that circadian clocks were well synchronized across body tissues, with genome-wide 24-hour rhythmicity in gene expression occurring primarily as morning and evening waves. Metabolic tissues showed the most rhythmicity and brain tissues the least. While this clock structure was conserved across all sexes and age groups, the authors found that overall gene expression rhythms were highly sex-dimorphic and more sustained in females. The number of rhythmic genes was nearly twice as high in females over males, particularly in adrenal gland and liver tissues. What’s more, Talamanca et al. found that the rhythmicity was generally lower in older individuals and notably in programs related to cardiovascular disease in the coronary arteries.