In a new study published in the journal Science, researchers exploring circadian molecular rhythms were able to uncover the organisation of gene expression rhythms in particular human tissues, and found that sex and age are involved, with females having a more regular pattern of rhythms.
In model organisms, analysing molecular rhythms is usually done using time-stamped measurements, but such data are not readily available in humans. To work around this, the researchers used existing measurements from a large cohort of post-mortem donors, combined with a novel computer algorithm that was designed to assign internal clock times to nearly one thousand donors.
“Interestingly, the data-science algorithm we developed turned out to resemble models from magnetic systems, which are well studied in statistical physics,” says study leader Felix Naef at Ecole Polytechnique Fédérale de Lausanne. Using this innovative approach, the researchers obtained the first comprehensive and accurate whole-organism view of 24-hour gene expression rhythms in 46 human tissues.
While the core clock machinery properties are conserved across the body and do not change significantly with sex and age, their analysis also revealed extensive programs of gene expression rhythms across major compartments of metabolism, stress response pathways and immune function, and these programs peaked twice a day.
In fact, the emerging whole-body organisation of circadian timing shows that rhythmic gene expression occurs as morning and evening waves, with the timing in the adrenal gland peaking first, while brain regions displayed much lower rhythmicity compared to metabolic tissues.
Dividing the donors by sex and age revealed a previously unknown richness of sex- and age- specific gene expression rhythms spread across biological functions. Strikingly, gene expression rhythms were sex-dimorphic (different in males and females) and more sustained in females, while rhythmic programs were generally reduced with age across the body.
Sex-dimorphic rhythms were particularly noticeable in the liver’s “xenobiotic detoxification,” the process by which liver breaks down harmful substances. Additionally, the study found that with age, the rhythm of gene expression decreases in the heart’s arteries, which may explain why older people are more susceptible to heart disease. This information could be useful in the field of “chronopharmacology,” which is the study of how a person’s internal clock affects the effectiveness and side effects of medication.
This study provides new insights into the complex interplay between our body clock, sex, and age. By understanding these rhythms, we might find new ways of diagnosing and treating pathologies such as sleep disorders and metabolic diseases.
