# Metformin to prevent inactivity-induced loss of muscle health during aging

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $13,437

## Abstract

Abstract
Hospitalizations for disease, injury, and/or surgery in older adults are likely to impair physical mobility and,
therefore, the older adults' capacity to be physically active both during hospitalization and beyond. The
resulting sedentary lifestyle is likely to be accepted as the “new normal”, ultimately increasing the risk of
skeletal muscle and metabolic dysfunction (e.g. insulin resistance and sarcopenia). Muscle atrophy and insulin
resistance are an unfortunate consequence with disuse in older adults. We have observed with our bed rest
studies in healthy older adults that in addition to muscle and metabolic changes, we notice increased skeletal
muscle inflammation, impaired glucose uptake signaling and an upregulation of enzymes related to de novo
ceramide biosynthesis. The accumulation of ceramide, a toxic lipid intermediate, can disrupt glucose
homeostasis and impair muscle growth. Metformin treatment has been shown to improve insulin sensitivity and
attenuate muscle loss in insulin resistant adults through a mechanism that may involve ceramide synthesis.
Metformin used as a preventive strategy to maintain muscle and metabolic health during a period of physical
inactivity in older adults has not been investigated. Therefore, I have proposed to conduct a clinical study in
older adults to test whether metformin treatment during bed rest will attenuate insulin resistance, muscle loss
and accumulation of ceramides. These findings will be foundational in the development of novel treatments,
such as metformin, to prevent insulin resistance and muscle atrophy in older adults during disuse periods. In
addition to gathering key preliminary data to inform future large scale clinical trials elucidating the muscle
protective effects of metformin during disuse, this research project will be linked to specific PhD training
experiences, such as the acquisition of new clinical and laboratory skill sets (i.e. coordinating a randomized
controlled trial, hyperinsulinemic euglycemic clamps, ceramide analysis methodology) and one-on one
interdisciplinary mentoring experiences in aging and skeletal muscle metabolism. Together, this training plan
will be a critical stepping stone in the development of my independent research career.

## Key facts

- **NIH application ID:** 9879697
- **Project number:** 5F31AG059438-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Alec Iain McKenzie
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $13,437
- **Award type:** 5
- **Project period:** 2018-04-05 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9879697

## Citation

> US National Institutes of Health, RePORTER application 9879697, Metformin to prevent inactivity-induced loss of muscle health during aging (5F31AG059438-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9879697. Licensed CC0.

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