# Skeletal Muscle Molecular Drug Targets for Exercise-induced Cardiometabolic Health

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $764,041

## Abstract

Skeletal Muscle Molecular Drug Targets for Exercise-induced Cardiometabolic Health
 The health benefits of exercise training are substantial, summarized in the Physical Activity Guidelines
Advisory Committee Report, and incorporated into the Physical Activity Guidelines for Americans in both 2008
and 2018. Understanding the mechanisms whereby exercise mediates its effects will have two major benefits.
It will promote an understanding how to tailor exercise programs to an individual’s specific clinical needs—
personalized lifestyle medicine. Also, it will provide critical information for the development of new therapeutics
for the myriad of health conditions exercise treats so well. It is likely that exercise—like many environmental
bodily exposures—induces epigenetic modifications directing gene expression, protein expression and
metabolic responses in target organs whereby exercise mediates its effects. Adaptations in skeletal muscle to
exercise training mediate many of the health benefits of exercise. However, how these beneficial effects are
mediated are little understood. It is the purpose of this project to understand these processes in three human
STRRIDE cohorts containing a broad range of seven different exercise exposures—and inactive control—with
extensive clinical, physiologic data paired with a biorepository of blood and skeletal muscle samples. The
hypothesis driving this work is that epigenetic modifications in skeletal muscle—serves a mediator and
integrator over time— DNA chromatin methylation—drives a major biological program mediating improvement
in cardiometabolic health in humans undergoing exercise training. Our work will be conducted in three specific
aims. 1) Determine the time course of the effects of exercise training and subsequent detraining on the
human skeletal muscle epigenome, transcriptome, proteome and metabolome. This will be approached
through classical associative modeling. Although we know that some DNA methylation targets and
downstream molecular signaling are responsive to a single bout of exercise, we do not know how long these
modifications persist; how they might integrate responses of single exercise bouts, and how they are related to
other downstream molecular targets at the epigenome, transcriptome, proteome and metabolome levels. 2)
Determine the specific and differential effects of exercise amount (dose), intensity and mode on the
human skeletal muscle methylome and downstream molecular signaling pathways on important
physiologic and clinical outcomes. In order to understand the pathways mediating exercise effects on
human health, it is important to relate the specific effects of exercise characteristics on molecular determinants
of exercise responsiveness with a focus on dose-response relationships. This aim will be approached through
a team-science approach involving causal modeling and regulatory circuits and known regulatory networks—stable
dynamic networks—consistent with the known literature ge...

## Key facts

- **NIH application ID:** 10212161
- **Project number:** 1R01HL153497-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** WILLIAM E KRAUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $764,041
- **Award type:** 1
- **Project period:** 2021-04-20 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212161

## Citation

> US National Institutes of Health, RePORTER application 10212161, Skeletal Muscle Molecular Drug Targets for Exercise-induced Cardiometabolic Health (1R01HL153497-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212161. Licensed CC0.

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