# Circadian clock and dietary restriction

> **NIH NIH R01** · CLEVELAND STATE UNIVERSITY · 2021 · $304,425

## Abstract

Calorie restriction (CR) was shown to extend longevity in many organisms; however, the mechanisms of CR are still
mostly unknown. In our previous study we found that the circadian clock is an important component of CR mechanisms
in mammals. We established that CR regulates expression of the circadian clock genes by controlling activity of circadian
transcriptional regulators BMAL1 and CRY1. In agreement with that, BMAL1 is necessary for the full metabolic benefits
of CR including lifespan extension. Indeed, we found that BMAL1 negatively regulates activity of mTORC1, which is
implicated in the regulation of aging and CR-mediated increase in longevity. We will continue the study by exploring our
hypothesis that circadian clock recruitment is essential for resource allocation and the full beneficial effects of CR on
physiology; in particular, CR recruits the circadian clocks by regulating the level and activity of CRY1 and BMAL1
proteins, which in turn contributes to differential regulation of mTORC1 and mTORC2. We will explore the hypothesis
through three specific aims. Aim 1. To decipher the mechanisms of regulation of the circadian clock gene expression by
CR. Aim 2. To investigate circadian clock-mediated mechanisms of CR-imposed effects on mTORC1 and mTORC2
activity and signaling. Aim 3. To dissect the effects of periodic feeding with or without reduced calorie intake on CR-
induced metabolic changes and longevity.

## Key facts

- **NIH application ID:** 10109958
- **Project number:** 5R01AG039547-10
- **Recipient organization:** CLEVELAND STATE UNIVERSITY
- **Principal Investigator:** Roman V Kondratov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $304,425
- **Award type:** 5
- **Project period:** 2011-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109958

## Citation

> US National Institutes of Health, RePORTER application 10109958, Circadian clock and dietary restriction (5R01AG039547-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10109958. Licensed CC0.

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