Navigation Links
'Marathon mice' elucidate little-known muscle type

Researchers report in the January issue of the journal Cell Metabolism, published by Cell Press, the discovery of a genetic "switch" that drives the formation of a poorly understood type of muscle. Moreover, they found, animals whose muscles were full of the so-called IIX fibers were able to run farther and at higher work loads than normal mice could.

The findings could ultimately lead to novel drugs designed to change the composition of muscle, the researchers said. Such treatments might have the potential to boost physical strength and endurance in patients with a variety of muscle wasting conditions.

The research team, led by Bruce Spiegelman of Harvard Medical School, found that increasing activity of the gene known as PGC-1â in the skeletal muscles of mice caused them to become crowded with IIX muscle fibers, which are normally much less prevalent.

"One reason why less is known about IIX fibers is that no one muscle group is packed with them," Spiegelman said. "For the first time, we have a mouse model very enriched in IIX fibers. These mice show a greatly increased capacity to sustain physical activity."

Skeletal muscle converts chemical energy into motion and force, ranging from rapid and sudden bursts of intense activity to continuous low-intensity work, the researchers said. At one functional extreme, muscles such as the soleus--a broad, flat muscle found in the calf of the leg--perform slow but steady activities such as maintaining posture. At the other extreme, muscles such as the quadriceps typically perform intense and rapid activities.

To fulfill these varied roles, muscles vary in their proportion of "slow-twitch" muscle fibers (types I and IIA), ideal for slow and constant roles, and "fast-twitch" fibers (type IIB), better suited to rapid and sudden activity of shorter duration. The fiber types are defined by which "myosin heavy chains" (MHCs) they contain and by their metabolic capacity, a feature larg ely determined by the number of energy-producing mitochondria they house. Myosins are motor proteins that consist of both "heavy" and "light" amino acid chains.

While most muscles in mammals contain a mixture of slow- and fast-twitch fiber types, some muscle beds are enriched for one type or the other, Spiegelman said. However, adult skeletal muscles also contain fibers with an abundance of a fourth MHC, type IIX, about which much less is known.

IIX fibers seem to have the oxidative metabolism of slow-twitch fibers mixed with the biophysical properties of fast-twitch fibers. Oxidative metabolism is by far the most efficient way of generating energy, Spiegelman said.

In the current study, the researchers produced mice with higher than normal levels of the transcriptional coactivator PGC-1â in their skeletal muscles. Transcriptional coactivators work with other cellular factors and machinery to control the activity of other genes. While earlier studies had found that the related coactivator PGC-1â plays a role in determining muscle type, the role of PGC-1â wasn't known.

"The muscle from the PGC-1â transgenic mice was strikingly redder in appearance than wild-type controls," indicative of their increased mitochondrial content, the researchers now report. Upon further examination, the researchers were surprised to find that the fibers showed a reduction in I, IIA, and IIB MHCs and as much as a 5-fold increase in IIX MHC.

Nearly 100% of muscle fibers in the transgenic animals contained abundant MHC IIX mRNA and protein, they found, as compared to only 15%?0% in normal animals. PGC-1â also changed the muscles' metabolic characteristics by driving the activity of genes that spark proliferation of mitochondria.

The PGC-1â animals with more IIX muscle fibers showed a greater capacity for aerobic exercise, they found. Transgenic mice were able to run, on average, for 32.5 min to exhaustion, compared to 26 min for t heir normal littermates, Spiegelman's group reported.

"These data have potential importance for the therapy of a number of muscular and neuromuscular diseases in humans," Spiegelman's group concluded.

"Many conditions accompanied by loss of physical mobility, including paraplegia, prolonged bed rest, and muscular dystrophies, involve a loss of oxidative fibers and their replacement with glycolytic fibers. This, in turn, results in a further loss of resistance to fatigue, exacerbating the patient's condition in a downward spiral. The identification of PGC-1â as a potential mediator of the development of oxidative type IIX fibers suggests new ways to modulate muscle fiber type in health and disease."
'"/>

Source:Cell Press


Related biology news :

1. Regenerating worms help elucidate stem cell biology
2. Scientists elucidate the kinome of key model organism
3. On the track of tiny larvae, a new model elucidates connections in marine ecology
4. Mirrors in the mind: New studies elucidate how the brain reflects onto itself the actions of others
5. Heart repair gets new muscle
6. Small worm yields big clue on muscle receptor action
7. New complete muscle grown in the lab
8. Spiders help scientists discover how muscles relax
9. Cant serve an ace? Could be muscle fatigue
10. Lance Armstrong through a physiological lens: hard training boosts muscle power 8%
11. Gene therapy for muscular dystrophy fixes frail muscle cells in animal model, Stanford study finds

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/8/2017)... -- Report Highlights The global biosurgery market ... in 2016 at a compound annual growth rate (CAGR) ... - An overview of the global market for biosurgery. ... 2015 and 2016, and projections of compound annual growth ... on the basis of product type, source, application, and ...
(Date:2/3/2017)... , Feb. 3, 2017  Texas Biomedical Research Institute announced ... Larry Schlesinger as the Institute,s new President and ... effective May 31, 2017. He is currently the Chair of ... the Center for Microbial Interface Biology at Ohio State University. ... the new President and CEO of Texas Biomed," said Dr. ...
(Date:2/1/2017)... 2017 IDTechEx Research, a leading provider of ... the availability of a new report, Sensors for Robotics: Technologies, ... Reading ... ... Source: IDTechEx Report "Sensors for Robotics: Technologies, Markets and Forecasts 2017-2027: ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... 24, 2017  OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), ... a Key Opinion Leader event to highlight new clinical ... poster presentation at the upcoming 2017 ASCO-SITC Immuno-Oncology Symposium ... will be held in-person and via live webcast on ... AM PST at the Lotte New York Palace Hotel ...
(Date:2/23/2017)... The Fight Against Cancer Innovation Trust (FACIT) and the ... report that Fusion Pharmaceuticals Inc. (Fusion) has closed a ... – JJDC, Inc. (JJDC) as the lead investor. Additional, ... and Genesys Capital, as well as founding investor FACIT.  ... ...
(Date:2/23/2017)...  Imanis Life Sciences announced today the launch ... viruses for virotherapy research. These viruses are licensed ... vaccinia virus-based technology platform for research use. ... partnership with Genelux to offer researchers, for the ... in research," said Dr. Kah Whye Peng ...
(Date:2/23/2017)... ... 23, 2017 , ... Today, researchers can fast-track sample collection ... and/or other biomarkers or SNPs of interest) using one, easy-to-collect saliva sample. With ... relationship between insulin and other relevant biomarkers can be extensively studied through a ...
Breaking Biology Technology: