# Muscle regulatory T cells in exercise and aging

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2022 · $69,802

## Abstract

PROJECT SUMMARY
An increase in human life expectancy without a proportional extension of time spent in good health, or “health
span,” has led to expansion of the global population of aged and frail individuals carrying multiple morbidities.
Chronic exercise improves health span in multiple model organisms. Such health span extension may be
underpinned by the anti-inflammatory effects of chronic exercise, which have been primarily identified through
measurements of changes in circulating cells and cytokines; however, tissue-resident immunocytes also play a
critical role in maintaining homeostasis and supporting stress responses; yet little is known about how tissue
immunophenotypes change with age or exercise. Recently, we have established mouse models of endurance
exercise that elicit rapid accumulation of immunocytes in skeletal muscle. This response shares many features
with the response to severe tissue injury, including accumulation of regulatory T cells (Tregs), which orchestrate
the transition from pro-inflammatory to repair processes. In an aged setting, function of tissue Tregs after injury
is reduced, contributing to the impaired muscle regeneration seen in old vis-à-vis young mice. A deeper
characterization of the relationship between exercise and muscle Treg activities is needed to improve our
understanding of the benefits of chronic exercise on muscle function and regenerative capacity. Thus, in the
current research plan, the overall goal is to understand the effects of exercise intervention in different phases of
life on age-associated changes in muscle function and immunocyte profiles. Aim 1 is designed to deepen our
characterization of immunocyte profiles and the functional importance of Tregs in acutely exercised muscle. We
postulate that acute exercise promotes muscle-specific accumulation of Tregs with unique transcriptional profiles
and that such accumulation supports maintenance of homeostasis in exercised muscle. In Aim 2, we will
elucidate and compare acute exercise-inducible changes in muscle biochemical and immunocyte profiles across
the mouse lifespan. We postulate that exercise-induced changes in muscle immunocyte profiles are sensitive to
age and that such age-associated changes in immunophenotype and function underpin impaired biochemical
adaptations of myofibers to exercise, worse control of inflammation, and increased muscle damage in old age.
Finally, in Aim 3, we will investigate the effects of chronic endurance exercise on age-related changes in muscle
function and biochemical and immunocyte profiles in mice. We postulate that chronic exercise protects against
age-related decline in muscle function and maintains “young” biochemical and immunocyte profiles in muscle.
Furthermore, we hypothesize that exercise preconditioning is prophylactic against subsequent muscular injury
and that such protection is mediated by augmented Treg function. If completed, this work will be the first
characterization of changes in exerc...

## Key facts

- **NIH application ID:** 10399435
- **Project number:** 5F32AG072874-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Paul Kent Langston
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,802
- **Award type:** 5
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399435

## Citation

> US National Institutes of Health, RePORTER application 10399435, Muscle regulatory T cells in exercise and aging (5F32AG072874-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399435. Licensed CC0.

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