# Synergistic Effects of Unacylated Ghrelin and Endurance Exercise on Sarcopenia and Mobility Loss

> **NIH AG R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2026 · $599,623

## Abstract

Project Summary/Abstract
Sarcopenia, the progressive loss of muscle mass and function, universally impacts the aging population,
contributing to loss of mobility and independence in older adults. With the rapid growth of the aging population,
there is an urgent need for effective strategies against sarcopenia. Exercise is the most effective intervention
that increases muscle mass and function in younger adults, but its benefits are attenuated in older adults due to
diminished responses to exercise training. Over the years, several candidate molecules, including metformin,
antioxidants, and resveratrol were combined with endurance exercise (EE) in an attempt to increase training-
induced benefits; however, these interventions failed to enhance training responses and, in some cases, reduced
the positive effects of exercise. Given metformin’s inhibitory effects on mitochondrial respiration and the ability
of antioxidants to scavenge signaling molecules in response to exercise, a logical next step is to combine EE
with a candidate molecule that specifically enhances mitochondrial bioenergetics and its downstream pathways.
A strong such candidate is unacylated ghrelin (UnAG), whose circulating levels are significantly decreased in
older adults and mice. Our pilot data provides evidence that UnAG combined with endurance exercise
(UnAG+EE) additively increases mitochondrial bioenergetics, while synergistically improving motor coordination,
muscle mass and contractile function. Our data also revealed that UnAG activated both shared (i.e., PGC-1α)
and distinct (i.e., mTORC2) pathways compared to those triggered by EE alone, suggesting that UnAG+EE may
provide synergistic and complementary benefits. Building on our compelling preliminary data, we hypothesized
that the combination of UnAG+EE will enhance mitochondrial bioenergetics and preserve NMJ integrity in older
mice, providing synergistic protection for sarcopenia. Our specific aims will focus on the effects of UnAG, EE,

## Key facts

- **NIH application ID:** 11306328
- **Project number:** 1R01AG092766-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Bumsoo  Ahn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AG
- **Fiscal year:** 2026
- **Award amount:** $599,623
- **Award type:** 1
- **Project period:** 2026-02-01T00:00:00 → 2031-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11306328

## Citation

> US National Institutes of Health, RePORTER application 11306328, Synergistic Effects of Unacylated Ghrelin and Endurance Exercise on Sarcopenia and Mobility Loss (1R01AG092766-01A1). Retrieved via AI Analytics 2026-07-07 from https://api.ai-analytics.org/grant/nih/11306328. Licensed CC0.

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