Abstracts & Literature Review 1

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Blood Flow Restriction Exercise Stimulates Mtorc1 Signaling and
Muscle Protein Synthesis in Older Men

Christopher S. Fry, Erin L. Glynn, Micah J. Drummond, Kyle L.Timmerman, Satoshi Fujita, Takashi Abe, Shaheen Dhanani, Elena Volpi, and Blake B. Rasmussen

JACO Editorial Reviewer: Neil L. Erickson, DC, DABCO, CCSP


Published:
Journal of the Academy of Chiropractic Orthopedists
September 2015, Volume 12, Issue 3
The original article copyright belongs to the original publisher. This review is available from:http://www.dcorthoacademy.org © 2015 (Erickson) and the Academy of Chiropractic Orthopedists. This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Author’s Abstract:

Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. J Appl Physiol 108: 1199 –1209, 2010. First published February 11, 2010;
doi:10.1152/japplphysiol.01266.2009.—

The loss of skeletal muscle mass during aging, sarcopenia, increases the risk for falls and dependence. Resistance exercise (RE) is an effective rehabilitation technique that can improve muscle mass and strength; however, older individuals are resistant to the stimulation of muscle protein synthesis (MPS) with traditional highintensity RE. Recently, a novel rehabilitation exercise method, low-intensity RE, combined with blood flow restriction (BFR), has been shown to stimulate mammalian target of rapamycin complex 1 (mTORC1) signaling and MPS in young men. We hypothesized that low-intensity RE with BFR would be able to activate mTORC1 signaling and stimulate MPS in older men. We measured MPS and mTORC1-associated signaling proteins in seven older men (age 70 + 2 yr) before and after exercise. Subjects were studied identically on two occasions: during BFR exercise [bilateral leg extension exercise at 20% of 1-repetition maximum (1-RM) with pressure cuff placed proximally on both thighs and inflated at 200 mmHg] and during exercise without the pressure cuff (Ctrl). MPS and phosphorylation of signaling proteins were determined on successive muscle biopsies by stable isotopic techniques and immunoblotting, respectively. MPS increased 56% from baseline after BFR exercise (P< 0.05), while no change was observed in the Ctrl group (P > 0.05). Downstream of mTORC1, ribosomal S6 kinase 1 (S6K1) phosphorylation and ribosomal protein S6 (rpS6) phosphorylation increased only in the BFR group after exercise (P> 0.05). We conclude that low-intensity RE in combination with BFR enhances mTORC1 signaling and MPS in older men. BFR exercise is a novel intervention that may enhance muscle rehabilitation to counteract sarcopenia.

Background: Resistance exercise training has been shown to be a beneficial intervention to protect against the effects of sarcopenia, with training studies showing increases in muscle protein synthesis and mass in both theold and young. However, the training studies often show a more robust muscle protein synthetic and strength response in the young than in the elderly.

Methods: The study included 7 elderly males who were randomly selected to the BFR or control groups. Health screening of the subjects included physical examination, stress test, laboratory tests, and ECG. DDimer blood tests were performed to predict the potential each subject had of developing thrombosis. The morning of the study a continuous infusion of phenylalanine was begun and maintained at a constant rate until the end of the experiment. A baseline strength test of one repetition leg (knee) extension was used to select the amount of weight to be used during the study. This value was 20% of the baseline amount. After a minimum of three weeks, the control group and the BFR group were switched so that all 7 subjects acted as both control and active study participants. In addition to measuring for muscle protein (mTORC1) signaling, the study also evaluated plasma lactate, plasma glucose, cortisol, and serum growth hormone. Leg circumference and oxygen saturation were also measured.

Results: Increases in plasma lactate, plasma glucose, cortisol, serum growth hormone, and muscle protein.

Conclusions: In the BFR group, there was also a significant increase in the phosphorylation of S6K1 and rpS6, suggesting enhanced mTORC1 signaling following exercise with BFR. The enhanced mTORC1 signaling is indicative of improved translation initiation, which likely explains the increase in muscle protein synthesis with BFR.

Clinical Relevance: It is useful for an aging population to be trained in the exercise methods that will provide the greatest return on their limited abilities to perform exercise.

JACO Editorial Summary:

The article was written by authors from the Division of Rehabilitation Sciences, Departments of Physical Therapy and Internal Medicine, Sealy Center on Aging, University of Texas Medical Branch, Galveston, Texas; where the research was conducted and Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan

  • The purpose of the study was to measure the increase in muscle protein synthesis in blood flow restricted muscles subjected to exercise.
  • Finding an exercise method that the elderly population can and will perform that gives maximum benefit for the maintenance of mobility would be a remarkable discovery.
  • The investigative researchers reported that muscle protein synthesis increased by 56% in the BFR group 3 hours after performance of a bout of lowintensity resistance exercise with BFR, while muscle protein synthesis did not increase in the Control group, who exercised without BFR.
  • The test group showed increases in plasma lactate, plasma glucose cortisol, growth hormone leg (thigh) circumference, and most importantly muscle protein synthesis.

Summary

There was some confusion during the initial reading of the article as it appeared that the “Infusion study 1” was a different group than the “BFR group”. Another area of confusion was how the researchers got arterialized blood from a vein. In the future the authors could be more succinct in referring to the thigh and leg (the portion below the knee) and the assignment of either flexion or extension at a joint (hip or knee) rather than the leg.

The idea of assisting the aging population with increased independence and lowered risks of disability is an admirable goal. However the methods studied in this case raise a number of concerns.

I tested the pain tolerance to the thigh pressure cuff of a number of patients in my office. I used an extra-large blood pressure cuff on the thigh of several patients who, without exception, reported significant pain when inflation reached the neighborhood of 160mm/Hg. I have difficulty accepting that the researchers used 200mm/Hg for a 4-5 minute period of time.

Cortisol is a hormone released in response to stress and it was found to be elevated in the test subjects. The researchers gave no explanation for this increased lab value. Increased cortisol inhibits the uptake of amino acids into the muscle cells, making it nearly impossible to fuel muscle cells and grow muscle. Two IV catheters were placed in each participant along with anesthesia for 5 muscle biopsies and the above mentioned pressure cuff for 4-5 minutes. Although the authors reported that “Subjects did not report any side effects immediately after exercise or 1 week after the infusion protocol” I am doubtful. Plasma lactate levels were increased after exercise in both the control and study group. While plasma lactate and lactic acid are not the same thing, my experience has shown that strenuous exercise will cause sore muscles in the 2-4 day period afterwards. Is it possible that the increased cortisol found in the subjects was a factor of pain and stress?

Knowing that all subjects were in both the test and control groups, I find it unusual that the researchers did not discuss the lowered baseline oxygen saturation in the test group.

Of the 18 proteins addressed in this study, 4 increased in both the study and control groups. It can well be said that the increases in the study group were greater, but for me, the degree of inconvenience of using the pressure cuff during exercise and potential discomfort associated therewith, is too great to justify its use, especially in the elderly patient.