Immune Function and Muscle Adaptations to Resistance Exercise in Older Adults
Condition: Sarcopenia; Aging; Immune Function
MeSH terms: Sarcopenia
Study type: Interventional

Summary: 
      The loss of muscle mass and strength due to aging leads to serious health problems for older
      adults. Muscle health can be improved by exercise training, but some people improve their
      strength substantially, whereas others improve little. The reason for this variation is
      unknown. This study will investigate whether function of the immune system influences how
      well people respond to exercise. Older Veterans who participate will have their muscle size,
      strength, and function measured periodically for almost a year. Participants will drink a
      nutritional supplement or placebo daily and complete a 36 session strength training program.
      Participants will be vaccinated for tetanus and donate small amounts of blood and muscle
      tissue during the study so that immune function can be compared to muscle outcomes during
      training and during a long-term follow-up. The study results should increase the
      investigators' understanding of the negative effects of aging on muscle and will possibly
      lead to better strategies for muscle maintenance and rehabilitation for older adults.
    

Detailed description: 
      Objective: The study will examine the influence of immune function in older adults on
      improvement of muscle mass, strength, and function by resistance training. The maintenance of
      those benefits during long term follow-up will also be examined. This objective will be
      accomplished by a double-blind randomized placebo-controlled trial of a nutritional
      supplement (Muscle Armor) which evidence suggests can improve immune function, promote muscle
      growth, and counteract muscle loss. The study premise is that aging results in decreased
      ability of the immune system to respond to stimuli such as exercise. The study proposes that
      the supplement will improve muscle health by promoting a shift in immune function of older
      adults from a pro-inflammatory state towards a state which supports muscle growth and
      maintenance.

      Research Plan: The study will randomize Veterans (age 60-80, N=50) to participate in the
      supplement or placebo groups in a three phase study. The phases of participation correspond
      to the three specific aims. Aim 1 will determine if 2-weeks of supplementation improves
      immune function. Humoral immune function will be assessed as the response to vaccination.
      Innate immune function will be measured as systemic and cellular responses to acute
      resistance exercise that the investigators' previous studies indicate are affected by aging.
      Aim 2 will determine if supplementation during 36 sessions of progressive high-intensity
      resistance training boosts improvement in muscle size (CT scan), strength, and function (gait
      and balance). Muscle adaptations at the cellular levels will also be measured. Aim 3 will
      determine if continued supplementation for 26-weeks after completion of exercise training
      promotes the retention of the gains in muscle size, strength, and function. Multivariable
      testing will then be used to compare the results between Aims 1, 2, and 3 to determine
      whether or not immune function is correlated with muscle adaptation to training or
      detraining.

      Methods: Participants will undergo nine blood draws and five muscle biopsies of the vastus
      lateralis over the course of the study so that the effects of the supplement on immune
      function and cellular adaptations to training can be measured. Three of the blood draws will
      be used to assess the antibody response to the tetanus, pertussis, and diphtheria vaccine.
      Muscle and blood will be collected before and after a bout of exercise conducted before and
      after the 2-weeks of supplementation prior to training. Immune function will be measured
      using the blood based on pro- and anti-inflammatory cytokine levels, the balance between
      specific T-cell subpopulations, and the proliferative capacity of mononuclear cells. Immune
      function will be measured in muscle based on macrophage content of specific cytokines and
      growth factors. The investigators' previous study showed that these muscle measures strongly
      correlate with size and strength gain after training. Key signaling pathways including
      nuclear factor-k B and PI3 kinase will also be measured. The fifth biopsy will be collected
      post-training to measure adaptation at the cellular level based on changes in number of
      satellite cells and myonuclei and fiber size. Hypotheses related to these measures will be
      tested with 80% power to detect at least 0.8 standard deviations difference in means between
      the supplement and placebo groups.

      Clinical Relevance: Exercise is clearly able to affect immune function. However, the proposed
      study will attempt to modulate immune function and determine the effects on exercise
      outcomes. The study will also examine detraining, an important issue for older adults, that
      is usually omitted from training studies. Thus, the study will potentially advance the
      understanding of the mechanisms of muscle gain and loss in older adults, but more
      importantly, the study will evaluate a nutritional intervention as a complement to exercise
      for supporting muscle health during aging. Targeting the immune system may be the advantage
      needed for an older Veteran to successfully maintain or restore the muscle mass, strength,
      and function that is necessary for personal independence.
    

Intervention name(s): TDAP; Acute Resistance Exercise; Resistance Exercise Training; Post-training Follow-up; Nutritional Supplement (Muscle Armor); Placebo (Kool-Aid)
Intervention type(s): Biological; Other; Other; Other; Dietary Supplement; Dietary Supplement
Intervention description(s): Both arms will receive the tetanus, diptheria, and pertussis vaccination after two weeks of treatment with supplement or placebo; Both arms will receive a single bout of resistance exercise twice, before and after two weeks of treatment with supplement or placebo, and be evaluated for the response within blood and muscle; Both arms will receive 36 sessions of progressive high-intensity resistance exercise training (thigh muscle) over the course of approximately 12 weeks.; Both arms will continue to receive treatment with supplement or placebo for approximately 26 weeks after completion of the exercise training. During this time subjects will not be allowed to perform resistance exercise.; Subjects in the supplement group will consume orange-flavored Muscle Armor according to the manufacturer's directions: one serving (approximately 30g, i.e. one scoop provided with the product by its manufacturer), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation.; Subjects in the placebo group will consume orange-flavored Kool-Aid (Kraft Foods) according to the manufacturer's directions: one serving (approximately 13g, i.e. one scoop provided with the product by the pharmacy), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation.
Other intervention name(s): tetanus, diptheria, and pertussis vaccination; Single bout of exercise; Chronic exercise; Detraining Period
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: resistance exercise; Juven; exercise training; interleukin-1; insulin-like growth factor