Mechanisms Underlying Local and Systemic Effects of Massage
Condition: Muscle Atrophy
MeSH terms: Muscular Atrophy; Atrophy
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether massage can attenuate the loss of muscle
      mass in humans after a short period of disuse.
    

Detailed description: 
      The loss of skeletal muscle mass is a common symptom associated with diseases such as cancer,
      AIDS, diabetes, and congestive heart failure, and with aging. Muscle atrophy is associated
      with poor disease prognosis and decreased quality of life and therefore, maintaining muscle
      size and reducing the loss of muscle during disuse atrophy is of vital significance.
      Mechanical stimulation of muscle, such as during resistance exercise, stimulates protein
      synthesis that increases muscle protein content, and muscle size. The investigators have
      shown that mechanical stimulation applied to skeletal muscle in the form of massage is an
      effective mechanotherapy in rats, since it leads to a shift in protein turnover favoring
      anabolism, attenuation of muscle loss and enhanced regrowth after disuse-induced atrophy.
      Whether the same positive effect of massage occurs in humans is currently unknown, but would
      be extremely beneficial for skeletal muscle and overall health in case where resistance
      exercise is contraindicated or not feasible. In addition to the direct anabolic effects on
      the massaged rat muscle, the investigators have shown an equally beneficial response on the
      homologous muscle in the contralateral non-massaged limb. This novel finding indicated the
      existence of indirect mechanisms that could have profound systemic effects beyond the
      massaged muscle. Extracellular vesicles (EVs) are lipid membrane-bound vesicles released from
      cells with the ability to modulate function of cells from which they are released, as well as
      in cells with which they fuse. As such EVs are likely mediators of the well-documented but
      poorly-understood effects of massage in humans on the brain and other organs, such as relief
      of pain, anxiety or depression or changes in immunity. Therefore, the goal of this proposal
      is to determine anabolic effects of massage in human muscle, and to identify whether EVs
      released with massage are candidates for beneficial effects of this mechanotherapy on muscle
      as well as other organs. In Aim 1 the investigators will address the following hypothesis:
      Massage acts as a mechanotherapy by attenuating muscle atrophy through a shift in protein
      biogenesis towards anabolism in humans. Using a novel massage device we will apply mechanical
      load to muscle undergoing atrophy through unilateral lower limb suspension and muscle size as
      well as protein synthesis and degradation will be determined. In Aim 2 the investigators will
      test the hypothesis that massage attenuates the loss of EVs during atrophy by enhancing EV
      biogenesis in muscle. The investigators will measure EVs and their miRNA cargo in the serum,
      and markers of EV biogenesis in muscle of human subjects from Aim 1. Results from this study
      will indicate not only whether mechanotherapy, such as massage, can attenuate atrophy and
      enhance anabolic processes during disuse, but also determine whether EVs are a candidate
      mechanism for the overall health benefits of massage.
    

Intervention name(s): Massage
Intervention type(s): Other
Intervention description(s): A custom-made cyclic compressive loading (CCL) device will be used to apply a mechanical load to the left thigh of the participants. Massage application using a 35 Newton load will be applied for 15 minutes every other day over the course of 7 days for a total of four massages.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Massage; Muscle; Extracellular Vesicles; Atrophy