Twelve-hour ultradian rhythmic reprogramming of gene expression in the human ovary during aging.

Abstract

Background: The 12-h ultradian rhythm plays a crucial role in metabolic homeostasis, but its role in ovarian aging has not been explored. This study investigates age-related changes in 12-h rhythmic gene expression across various human tissues, with a particular focus on the ovary.

Methods: We analyzed transcriptomic data from the GTEx project to examine 12-h ultradian rhythmic gene expression across multiple peripheral human tissues, exploring sex-specific patterns and age-related reprogramming of both 12-h and 24-h rhythmic gene expression.

Results: Our findings revealed sex-dimorphic patterns in 12-h rhythmic gene expression, with females exhibiting stronger 12-h rhythms than males. Midlife (ages 40-49) was identified as a critical period for the reprogramming of both 12-h and 24-h rhythmic gene expression. The ovary was notable among other organs due to its high number of genes exhibiting 12-h rhythmic expression and a distinct pattern of rhythmic gene expression reprogramming during aging. This reprogramming involved two gene subsets: one subset adopted de novo 12-h rhythms, while another subset shifted from 24-h rhythms in younger individuals to dual 12-h and 24-h rhythms in middle-aged individuals. Both subsets were primarily associated with angiogenesis.

Conclusions: This study is the first to report age-related reprogramming of 12-h rhythms in human tissues, with a particular focus on the amplification of 12-h rhythms in angiogenesis-related genes in the aging ovary. These findings provide novel insights into the mechanisms structured format of the abstract text underlying ovarian aging and suggest potential therapeutic strategies targeting rhythmic gene expression in the ovary.