Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial

R. Grace Walton, Cory M. Dungan, Douglas E. Long, S. Craig Tuggle, Kate Kosmac, Bailey D. Peck, Heather M. Bush, Alejandro G. Villasante Tezanos, Gerald McGwin, Samuel T. Windham, Fernando Ovalle, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p =.003) and thigh muscle mass (p <.001) than metformin. CT scan showed that increases in thigh muscle area (p =.005) and density (p =.020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p =.007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228.

Original languageEnglish
Article numbere13039
JournalAging Cell
Volume18
Issue number6
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
Funding information The study was funded by National Institute on Aging, Grant/Award Number: R01AG046920 and National Center for Advancing Translational Sciences, Grant/Award Numbers: UL1TR001998, UL1TR003096. The authors thank Janna R. Jackson, PhD (Center for Muscle Biology, University of Kentucky) for assistance with initial analyses and data management. We thank Zachary Johnson for exercise training data management and Jenny L. Martz for study coordination. The authors also wish to thank Michael J. Stec, PhD, Neil A. Kelly PhD, and Derek Wiggins, MS (UAB Center for Exercise Medicine, University of Alabama at Birmingham) for assistance with muscle biopsy processing.

Publisher Copyright:
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Keywords

  • aging
  • exercise–drug interaction
  • muscle mass
  • strength training

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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