# Project 1: Enhancing Circadian Signal to Improve Cardiometabolic Function in Aging

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2020 · $357,715

## Abstract

Decreased amplitude and stability of rhythmic behaviors, including the prominent fragmentation of sleep are
hallmarks of aging in humans. It is now established from both laboratory and field studies that disrupted
circadian function represents a significant risk factor for cardiometabolic disease (CMD) in humans. The
exciting evidence of the ubiquity of circadian clocks in all tissues, and their critical role in metabolism, not only
opens up new avenues for exploring the mechanistic interactions between central and peripheral clocks in
cardiometabolic aging, but also to develop therapeutic interventions to re-establish synchrony between central
and peripheral clocks with each other and with the external physical and social environments. Feeding has
been shown to synchronize clocks in peripheral tissues and animal studies have demonstrated that restricting
feeding to the active period decreases CMD risk, while in humans decreased caloric intake in the evening is
associated with a lower body mass index (BMI). The amplitude of melatonin (typically decreased with
advancing age), can be considered a marker of robustness of central circadian function, but melatonin also has
physiological effects beyond circadian regulation throughout the body. Recent observations have
demonstrated low melatonin levels are a risk factor for incident diabetes and hypertension independent of
sleep duration. Together, this data suggests that strategies aimed at synchronizing feeding behavior and
enhancing the nocturnal melatonin signal can positively impact cardiometabolic function in older adults. We
propose to take an innovative approach that combines the recent data on the role of feed/fast patterns on clock
regulated metabolic activity and the reemergence of scientific interest of the central and peripheral effects of
melatonin on cardiometabolic function to improve metabolic health in late middle to old age. The primary aim of
this project is develop translatable circadian based interventions that enhance synchronization of central and
peripheral rhythms, to ultimately improve cardiometabolic function and sleep quality in older adults. This project
will enroll 100 older adults (55-75 years) to participate in a parallel (4 arm intervention) placebo controlled
study to determine whether a 6 week program of extended overnight fasting (EOF) of 12-14 hours and/or low
dose (3 mg) melatonin administration will enhance circadian amplitude and improve cardiometabolic function,
as well as to evaluate the potential beneficial effects of a regimen that combines both treatments. The results
from this study will demonstrate novel circadian based clinically applicable approaches for maintaining
circadian-metabolic health in older age. In addition, the similarity of the baseline characteristics in Project 1
and Project 2, and the complementary physiological and molecular measures and analyses of clock genes and
NAD+ regulatory pathways across all 3 projects will allow us to study the...

## Key facts

- **NIH application ID:** 9969249
- **Project number:** 5P01AG011412-21
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Phyllis C. Zee
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,715
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969249

## Citation

> US National Institutes of Health, RePORTER application 9969249, Project 1: Enhancing Circadian Signal to Improve Cardiometabolic Function in Aging (5P01AG011412-21). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9969249. Licensed CC0.

---

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