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J Gerontol A Biol Sci Med Sci. 2021 Nov 15;76(12):2132-2140. doi: 10.1093/gerona/glab186.

Age-Related Susceptibility to Muscle Damage Following Mechanotherapy in Rats Recovering From Disuse Atrophy.

The journals of gerontology. Series A, Biological sciences and medical sciences

Zachary R Hettinger, Kyoko Hamagata, Amy L Confides, Marcus M Lawrence, Benjamin F Miller, Timothy A Butterfield, Esther E Dupont-Versteegden

Affiliations

  1. Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, USA.
  2. Center for Muscle Biology, University of Kentucky, Lexington, USA.
  3. Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, USA.
  4. Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, USA.

PMID: 34181006 PMCID: PMC8599051 DOI: 10.1093/gerona/glab186

Abstract

The inability to fully recover lost muscle mass following periods of disuse atrophy predisposes older adults to lost independence and poor quality of life. We have previously shown that mechanotherapy at a moderate load (4.5 N) enhances muscle mass recovery following atrophy in adult, but not older adult rats. We propose that elevated transverse stiffness in aged muscle inhibits the growth response to mechanotherapy and hypothesize that a higher load (7.6 N) will overcome this resistance to mechanical stimuli. F344/BN adult and older adult male rats underwent 14 days of hindlimb suspension, followed by 7 days of recovery with (RE + M) or without (RE) mechanotherapy at 7.6 N on gastrocnemius muscle. The 7.6 N load was determined by measuring transverse passive stiffness and linearly scaling up from 4.5 N. No differences in protein turnover or mean fiber cross-sectional area were observed between RE and RE + M for older adult rats or adult rats at 7.6 N. However, there was a higher number of small muscle fibers present in older adult, but not adult rats, which was explained by a 16-fold increase in the frequency of small fibers expressing embryonic myosin heavy chain. Elevated central nucleation, satellite cell abundance, and dystrophin-/laminin+ fibers were present in older adult rats only following 7.6 N, while 4.5 N did not induce damage at either age. We conclude that age is an important variable when considering load used during mechanotherapy and age-related transverse stiffness may predispose older adults to damage during the recovery period following disuse atrophy.

© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Keywords: Aging; Disuse atrophy; Extracellular matrix; Mechanotherapy; Skeletal muscle

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