# Enhancing Adaptations to Exercise

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $159,000

## Abstract

Our preliminary data implicates chronic inflammation as a factor that may lead to biochemical abnormalities in
muscle and attenuate some of the adaptive responses to exercise. The objective of this project is to evaluate
a hypothesis that chronic inflammation originating from inflamed adipose tissue triggers inflammatory
responses within skeletal muscle, leading to oxidative stress, reduced mitochondrial capacity, compromised
muscle quality, functional and metabolic impairments, and attenuated adaptive responses to exercise.
Aim 1 will determine the impact of chronic inflammation on skeletal muscle physiology.
Skeletal muscle biochemical and functional parameters will be compared in older adults grouped into quartiles
based on a composite systemic inflammatory score. Muscle biopsies will be used to evaluate muscle-specific
inflammatory responses (TLR4, NLRP3), mitochondrial function (respiratory capacity, oxidant emissions,
coupling efficiency), and the impact on the quality of the muscle proteome (mass spectrometry). Adipose
tissue inflammation and abundance of senescent cells will be determined from subcutaneous abdominal
adipose tissue biopsies. Functional outcomes will include muscle mass, strength, fatigue, whole-muscle
oxidative capacity, and glucose metabolism. Outcomes will be measured again following 24 weeks of placebo
or eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) to reduce adipose tissue inflammation.
Aim 2 will determine the impact of chronic inflammation on responsiveness to acute exercise.
Responsiveness to a single bout of exercise will be compared across inflammation quartiles. Exercise
responsiveness will be determined from the induction of muscle protein synthesis and changes in putative
transcriptional and proteomic signals known to regulate exercise adaptations in skeletal muscle. Outcomes will
be measured again following 24 weeks of placebo or n3-PUFAs to reduce adipose tissue inflammation.
The contribution of the proposed research is expected to be a detailed understanding of the mechanistic links
between systemic inflammation, adipose tissue inflammation, and local inflammatory responses within aging
muscle. This work will also lead to new insights into the influence of chronic inflammation on biochemical and
functional parameters in aging skeletal muscle and responsiveness to acute exercise. The knowledge gained
in the proposed study will have a positive impact because “exercise resistance” represents a significant barrier
to the prevention and reversal of disease and disability in humans, and understanding the role of inflammation
in skeletal muscle physiology may lead to new approaches to enhance the beneficial adaptations to exercise in
populations that stand to benefit most. Discovering new ways to enhance training responses in people,
particularly those at risk for sarcopenia and related metabolic disorders, will have significant benefit since
exercise non-responders have increased risk for metabolic disea...

## Key facts

- **NIH application ID:** 10080916
- **Project number:** 3R01AG054454-03S1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** IAN R LANZA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $159,000
- **Award type:** 3
- **Project period:** 2017-09-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080916

## Citation

> US National Institutes of Health, RePORTER application 10080916, Enhancing Adaptations to Exercise (3R01AG054454-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10080916. Licensed CC0.

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