Exercise research traditionally has focused on the effects of training, rather than underlying genetic mechanisms. But physiologists wondered what would happen if they took a single strain of rats – meaning they all had the same basic genetic background – and bred two separate lines purely on the basis of "continued selecting of untrained rats with either high- and low-running endurance." In this way, they could study the genetic role in endurance performance and oxygen delivery systems.
Results of this large longitudinal study have been coming out generation by generation, and now a group of researchers at the University of California, San Diego have found some surprising results at generation #15 (G15), compared with G7. The G7 untrained rats from the "athletic" line had a greater running endurance and increased oxygen consumption (12%) than the "couch potatoes." These differences were mainly due to peripheral improvements (skeletal muscle) rather than central physiological changes in the cardiovascular or respiratory systems.
Wider endurance, oxygen usage differences reflect system-wide changes
As would be expected, the UCSD physiologists found that the continued selection led to significantly greater differences in endurance and oxygen consumption (44%) between the two groups of G15 rats than were seen at G7.
"This enhanced divergence at G15 was due in part to an increased skeletal muscle oxygen conductance that allowed for better transport of the oxygen to the muscle mitochondria of the athletic rats." according to Richard A. Howlett, lead author of one of three papers on the experiment. Howlett and the other two lead authors, Scott D. Kirkton and Patrick G. Giuliano are all from UCSD's Department of Medicine, Division of Physiology.
They are presenting their research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005. (See below * for specifics.)
Howlett continued: "However, we found that in addition the G15 'athletic' rats had increased performance due to central changes in oxygen delivery." Specifically, the running rats had improved cardiovascular systems (proportionally larger hearts (16% ) and increased blood flow (33%), reported in Kirkton et al., below) and respiratory systems (proportionally larger lungs (17%) and better oxygen diffusing capacity, reported in Giuliano et al., below) over the G7 stage, the researchers pointed out.
Oxygen delivery system maximized over time; support for 'controversial thesis'
Overall, Kirkton said the G15 results are exciting because "they clearly demonstrate that steps in the oxygen delivery system are coordinated to maximize efficiency, independent of exercise or other environmental influences." And by the G15 stage, the central delivery components (lung and cardiovascular system) have improved to better meet the demands of the muscles. "Additionally, our results provide support for the controversial hypothesis that suggests that physiological systems, such as the oxygen delivery pathway, are, over time, optimized in animals," Kirkton noted.
Next steps and implications for human attitudes and therapies
Having demonstrated the genetic role in endurance performance and the oxygen delivery systems, the group of researchers are turning their attention to identify the various genes involved that provide the underlying signal for "why" some subjects become more athletic, while others are couch potatoes.
This effort will include looking for genes and/or signaling mechanisms that prompt the initial signal for the differential abilities to run on a treadmill without training, as well as the mechanisms responsible for the "natural" improvements in muscular, cardiovascular and pulmonary oxygen delivery.
Further in the future the physiologists hope that identifying these genes and underlying processes could provide insight into human attitudes toward exercise and lead to therapies to improve oxygen delivery in patients with muscular, cardiovascular and respiratory diseases.
*Paper presentations: These research results reflect three concurrent presentations at IUPS. Each is listed below with the lead author. Other authors involved in all three papers are listed below. The authors will be in attendance 12:30 p.m.-3 p.m. Tuesday April 5, Physiology session 936, Physiological genomics of the respiratory system. Their boards, A487-A489, will be on view 7:30 a.m. - 4 p.m.
"VO2max and muscle O2 transport in rats continue to diverge with further selective breeding for endurance running." Richard A. Howlett, University of California at San Diego. 936.2/A488.
"Cardiovascular differences between rats selectively bred for endurance running capacity." Scott David Kirkton, UCSD, 936.3/A489.
"15 generations of selective breeding for endurance running capacity in rats is associated with enhanced lung structure and function not seen at generation 7." Patrick G. Giuliano (this paper only), UCSD. 936.1/A487.
Others involved in all three papers: Peter D. Wagner, Harrieth E. Wagner, UCSD Department of Medicine, Division of Physiology (as are Howlett, Kirkton and Giuliano); Norberto C. Gonzalez, University of Kansas Medical Center, Dept. of Molecular and Integrative Physiology; Steven L. Britton and Lauren G. Koch, University of Michigan Dept. of Physical Medicine and & Rehabilitation.
Funding. Research was supported by the National Institutes of Health.
The 35th Congress of the International Union of Physiological Sciences is in San Diego, March 31 - April 5, 2005. The Congress (http://www.iups2005.org/) is organized by the six member societies of the U.S. National Committee of the IUPS, the American Physiological Society, the Society for Neuroscience, the Microcirculatory Society, the Society of General Physiologists, the Biomedical Engineering Society, and the Society for Integrative and Comparative Biology, under the auspices of the U.S. National Academy of Sciences.
The IUPS conference, held every four years, runs concurrently this year with Experimental Biology 2005 at the San Diego Convention Center.
The American Physiological Society (APS), which is hosting IUPS, was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes nearly 4,000 articles every year in its 14 peer-reviewed journals. In May, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).
Editor's Note: For further information or to schedule an interview with a member of the research team, please contact Mayer Resnick at the IUPS/APS newsroom @ 619.525.6228 (March 31-April 6), or 301.332.4402 (cell) or 301.634.7209 (office), or Stacy Brooks at 240.432.9697 (cell) or 301.634.7253 (office).
A searchable online program for IUPS and EB is at http://www.faseb.org/meetings/eb2005/call/default.htm
IUPS/APS Newsroom March 29-April 6
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