# Understanding rhythmic gene regulatory mechanisms in the mammalian circadian system

> **NIH NIH F31** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2022 · $39,688

## Abstract

Summary
 Circadian rhythms are biological, physiological, and behavioral processes that enable organisms to
respond to the environmental changes caused by the rotation of the Earth. Interestingly, recent data started to
shed light into the impact of aging on circadian rhythms. For example, circadian processes, such as melatonin
secretion and onset of sleep, are phase-advanced in the circadian cycle as humans age. Moreover, the
number of rhythmically expressed genes is reduced by 23% in old mouse liver compared to young mouse liver.
Furthermore, nearly half of mRNA expressed rhythmically in old mouse liver are not expressed rhythmically in
young mouse liver. These data clearly indicate that the aging process changes the molecular mechanisms that
drive rhythmic mRNA expression. However, it remains unclear how aging alters the number and identity of
rhythmically expressed mRNAs. The goal of this proposal is to understand how the molecular mechanisms that
regulate rhythmic gene expression are altered with age and what impact aging has on the circadian cycle.
Successful accomplishment of the proposed project will uncover age-related changes to the mechanisms that
drive circadian gene expression that are thought to play key roles in driving and maintaining circadian rhythms
of various downstream biological processes. For an mRNA to be rhythmically expressed; synthesis,
degradation, or a combination of the two must be rhythmic. Additionally, the average mRNA half-life must be
short enough for RNA to be newly synthesized each day. In Aim 1, we will experimentally measure circadian
changes of mRNA expression, mRNA synthesis and degradation rates both in young and old mouse
fibroblasts to evaluate which of these processes is most susceptible to age-related changes in driving rhythmic
gene expression. In Aim 2, we will bioinformatically measure circadian changes of mRNA expression, mRNA
synthesis degradation rates in fly brain by leveraging circadian RNA-seq datasets that are publicly available.
Identification of age-related changes in driving circadian gene expression can ultimately help us develop
diagnostic tools and intervention strategies to mitigate circadian disturbances with age. Modern lifestyles
contain many stimuli that disrupt the core-clock mechanism such as bright light at night from phones, jet-lag,
and night shift work. It is critical that we understand how the mechanisms that drive circadian rhythms change
with age to prevent circadian dysregulation that may be exacerbated with age.

## Key facts

- **NIH application ID:** 10378498
- **Project number:** 5F31AG071393-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Benjamin Unruh
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,688
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378498

## Citation

> US National Institutes of Health, RePORTER application 10378498, Understanding rhythmic gene regulatory mechanisms in the mammalian circadian system (5F31AG071393-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10378498. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*