Randomized, Four-Arm, Dose-Response Clinical Trial to Optimize Resistance Exercise Training for Older Adults With Age-Related Muscle Atrophy

Exp Gerontol. 2017 Dec 1;99:98-109. doi: 10.1016/j.exger.2017.09.018. Epub 2017 Sep 28.


Purpose: The myriad consequences of age-related muscle atrophy include reduced muscular strength, power, and mobility; increased risk of falls, disability, and metabolic disease; and compromised immune function. At its root, aging muscle atrophy results from a loss of myofibers and atrophy of the remaining type II myofibers. The purpose of this trial (NCT02442479) was to titrate the dose of resistance training (RT) in older adults in an effort to maximize muscle regrowth and gains in muscle function.

Methods: A randomized, four-arm efficacy trial in which four, distinct exercise prescriptions varying in intensity, frequency, and contraction mode/rate were evaluated: (1) high-resistance concentric-eccentric training (H) 3d/week (HHH); (2) H training 2d/week (HH); (3) 3d/week mixed model consisting of H training 2d/week separated by 1 bout of low-resistance, high-velocity, concentric only (L) training (HLH); and (4) 2d/week mixed model consisting of H training 1d/week and L training 1d/week (HL). Sixty-four randomized subjects (65.5±3.6y) completed the trial. All participants completed the same 4weeks of pre-training consisting of 3d/week followed by 30weeks of randomized RT.

Results: The HLH prescription maximized gains in thigh muscle mass (TMM, primary outcome) and total body lean mass. HLH also showed the greatest gains in knee extension maximum isometric strength, and reduced cardiorespiratory demand during steady-state walking. HHH was the only prescription that led to increased muscle expression of pro-inflammatory cytokine receptors and this was associated with a lesser gain in TMM and total body lean mass compared to HLH. The HL prescription induced minimal muscle regrowth and generally lesser gains in muscle performance vs. the other prescriptions.

Major conclusions: The HLH prescription offers distinct advantages over the other doses, while the HL program is subpar. Although limited by a relatively small sample size, we conclude from this randomized dose-response trial that older adults benefit greatly from 2d/week high-intensity RT, and may further benefit from inserting an additional weekly bout of low-load, explosive RT.

Trial registration: ClinicalTrials.govNCT02442479.

Keywords: Aging; Exercise; Exercise dose; Muscle inflammation; Muscle mass; Muscle strength.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorptiometry, Photon
  • Age Factors
  • Aged
  • Aging
  • Alabama
  • Cardiorespiratory Fitness
  • Dietary Supplements
  • Female
  • Gene Expression Regulation
  • Geriatric Assessment
  • Humans
  • Isometric Contraction*
  • Male
  • Middle Aged
  • Muscle Fatigue
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle Strength*
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology*
  • Muscular Atrophy / diagnostic imaging
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / physiopathology
  • Muscular Atrophy / therapy*
  • Recovery of Function
  • Resistance Training / adverse effects
  • Resistance Training / methods*
  • Time Factors
  • Treatment Outcome
  • Whey Proteins / administration & dosage


  • Muscle Proteins
  • Whey Proteins

Associated data

  • ClinicalTrials.gov/NCT02442479
  • ClinicalTrials.gov/NCT02442479