Maximizing Mechanisms of Muscle Hypertrophy to Combat Sarcopenia in Older Adults
Condition: Aging; Muscular Atrophy
MeSH terms: Sarcopenia; Muscular Atrophy; Hypertrophy
Study type: Interventional

Summary: 
      Resistance training has shown the most promise among interventions aimed to combat aging
      muscle atrophy as it enhances strength, power, and mobility function, but induces varying
      degrees of skeletal muscle hypertrophy as the investigators demonstrated in the initial
      5-year funding period of this award (2001-2006). In the subsequent 5-year funding period
      (2007-2012), the investigators built on this prior work by using a dose-response approach in
      older adults - ultimately to optimize the treatment of age-related muscle atrophy. The
      investigators tested four, long-term resistance training prescriptions in older (60-75 yr)
      women and men to determine which prescription maximizes mechanisms driving muscle regrowth.
      One of the innovations in this project was the use of a 4-wk pre-training program to reach a
      plateau in the early, non-muscle mass adaptations, thereby establishing a true baseline from
      which both mechanisms of measurable muscle hypertrophy and functional consequences of
      hypertrophy could be studied in a tightly integrated fashion without bias in the subsequent
      experimental period. A randomized design was used to test the overarching hypothesis that a
      novel program of mixed strength and power training would optimize the anabolic environment to
      promote muscle hypertrophy and robust gains in performance. This hypothesis was tested with
      three specific aims.
    

Detailed description: 
      Resistance training has shown the most promise among interventions aimed to combat aging
      muscle atrophy as it enhances strength, power, and mobility function, but induces varying
      degrees of skeletal muscle hypertrophy as we demonstrated in the initial 5-year funding
      period of this award (2001-2006). In the subsequent 5-year funding period (2007-2012), we
      built on this prior work by using a dose-response approach in older adults - ultimately to
      optimize the treatment of age-related muscle atrophy. We tested four, long-term resistance
      training prescriptions in older (60-75 yr) women and men to determine which prescription
      maximizes mechanisms driving muscle regrowth (protein synthesis and myonuclear addition). One
      of the innovations in this project was the use of a 4-wk pre-training program to reach a
      plateau in the early, non-muscle mass adaptations, thereby establishing a true baseline from
      which both mechanisms of measurable muscle hypertrophy and functional consequences of
      hypertrophy could be studied in a tightly integrated fashion without bias in the subsequent
      experimental period. A randomized design was used to test the overarching hypothesis that a
      novel program of mixed strength and power training would optimize the anabolic environment to
      promote muscle hypertrophy and robust gains in performance. This hypothesis was tested with
      three specific aims.

      Specific Aim 1. We determined the effects of manipulating intensity, recovery, and mode of
      contraction on rates of muscle hypertrophy and muscle mass-dependent improvements in tests of
      in vivo muscle performance among older women and men. In brief, the four training models
      were: (1) traditional high-resistance concentric-eccentric training (H) 3 d/wk (HHH3); (2)
      high-resistance concentric-eccentric training 2 d/wk (HH2); (3) 3 d/wk mixed model consisting
      of high-resistance concentric-eccentric training 2 d/wk separated by 1 bout of
      low-resistance, high-velocity, concentric only training (L) (HLH3); and (4) 2 d/wk mixed
      model consisting of high-resistance concentric-eccentric training 1 d/wk and low-resistance,
      high-velocity, concentric only training 1 d/wk (HL2). For Aim 1, we hypothesized that the
      HLH3 prescription would prove optimal overall for combined gains in muscle mass, strength,
      power, and fatigue resistance in both women and men, while HL2 would be the least effective
      program due to insufficient weekly loading.

      Specific Aim 2. Myofiber hypertrophy requires net muscle protein synthesis, and advanced
      fiber expansion is facilitated by nuclear addition. We are conducting a comprehensive
      evaluation of: (1) key regulatory steps in the protein synthesis/degradation machinery; and
      (2) myonuclear addition and satellite cell activation/cell cycle regulation. Quantitative
      relationships between metabolic/molecular responses and the magnitude of muscle hypertrophy
      among older adults will enable us to identify underlying factors that respond differently to
      these four resistance training models, potentially in a gender-specific manner, thus
      revealing important processes that drive the hypertrophy adaptation. We hypothesized that
      muscle protein synthesis and myonuclear addition, along with key underlying regulatory
      processes, would be most favorably affected by the work-recovery cycle of 2 d/wk
      high-resistance loading (HLH3 and HH2 models), thereby optimizing the anabolic environment
      for muscle hypertrophy in both older women and men.

      Specific Aim 3. To translate the findings under Aim 1 to clinically important outcomes, we
      determined the degree to which non-traditional resistance training programs lead to
      improvements in mobility function and weight-bearing exercise difficulty. We hypothesized
      that a less stressful weekly training regimen consisting of fewer high-resistance
      contractions (HLH3) and/or fewer training sessions (HH2) while achieving substantial
      hypertrophy would promote equal or better improvements in mobility function and
      weight-bearing exercise difficulty than the traditionally prescribed HHH3 program.
    

Intervention name(s): resistance training
Intervention type(s): Behavioral
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: exercise; resistance training; muscle strength; muscle hypertrophy