New culprit in muscle defects, insulin resistance that come with age

May 4, 2010

Type 2 diabetes is a widespread problem for many people these days, and our risk for insulin resistance and diabetes only grows as we age. Now, a new report in the May issue of Cell Metabolism reveals a new contributor to the problem: The muscles of elderly people and of people with type 2 diabetes contain lower concentrations of a protein known as PARL (short for "presenilin-associated rhomboid-like").

PARL plays an important role within cells in remodeling power-generating mitochondria. It's PARL's job to oversee mitochondria's quality control, specifically by maintaining their integrity as the cellular components undergo normal processes of fission and fusion.

The findings provide yet another link between insulin resistance and the function of mitochondria, the researchers say.

When mitochondria aren't functioning properly, food doesn't get metabolized to the level that it should, explained Anthony Civitarese of Pennington Biomedical Research Center. Instead of getting burned, fats accumulate in cells where they impair insulin's action. As mitochondria fail to work efficiently, they also produce more damaging free radicals.

In the new study, Civitarese's team wanted to follow up on previous clues that PARL might play a role in mitochondrial abnormalities and insulin resistance. To do that, they examined PARL expression levels in the muscles of healthy young people compared to elderly people. Importantly, they specifically compared young and elderly people who were similar to one another in other respects, including their , fatty acid and glucose levels, and physical activity levels.

Relative to younger people, older people showed signs of insulin resistance. They also had fewer numbers of mitochondria and lower expression of the PARL gene.

Follow-up studies in mice showed that treatments designed to lower PARL levels in muscle led to fewer mitochondria, reductions in other important , and reduced . Studies in human muscle cells showed essentially the same thing, the researchers report.

"These overlapping answers point to a common mechanism for insulin resistance and the defects that come with aging," Civitarese said.

Together with earlier evidence, the findings show "that lower PARL expression is an early defect altering mitochondrial function and insulin resistance in response to a metabolic challenge," the researchers wrote. "We hypothesize that impaired PARL function is an important risk factor for the development of insulin resistance in skeletal muscle by decreasing mitochondrial mass and energetics and increasing oxidative stress, thus contributing to impaired glucose metabolism. As continues to develop, mitochondrial function, oxidative damage, and PARL activity may decline further, leading to a vicious cycle that eventually contributes to the development of T2DM or other age-associated diseases, including sarcopenia," a loss of muscle mass and strength.

Civitarese said it's not clear why PARL levels decline with age, but the findings suggest that increasing PARL levels may bring metabolic benefits. There is some possibility that PARL could be used as a drug or drug target, but he cautions that such a path would likely be difficult. That's because PARL does its work in a hard-to-reach place-- inside mitochondria, which are encapsulated in a double membrane.

Explore further: Power-boosting signal in muscle declines with age

More information: Ravussin et al.: “Regulation of Skeletal Muscle Oxidative Capacity and Insulin Signaling by the Mitochondrial Rhomboid Protease PARL.” Publishing in Cell Metabolism 11, 412-426, May 5, 2010. DOI:10.1016/j.cmet.2010.04.004

Related Stories

Power-boosting signal in muscle declines with age

February 6, 2007

As people age, they may have to exercise even harder to get the benefits afforded to younger folk. That's the suggestion of a report in the February issue of the journal Cell Metabolism, published by Cell Press, showing that ...

Exercise pivotal in preventing and fighting type II diabetes

February 7, 2007

One in three American children born in 2000 will develop type II diabetes, according to the U.S. Centers for Disease Control and Prevention (CDC). A new study at the University of Missouri-Columbia says that acute exercise ...

Scientists Identify New Mechanism of Insulin Resistance

January 14, 2008

Resistance to insulin that precedes type 2 diabetes may stem from a "metabolic traffic jam" that blocks the body's ability to switch between glucose and fat as energy sources, say researchers at Duke University Medical Center.

Apelin hormone injections powerfully lower blood sugar

November 4, 2008

By injecting a hormone produced by fat and other tissues into mice, researchers report in the November Cell Metabolism that they significantly lowered blood sugar levels in normal and obese mice. The findings suggest that ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Cow embryos reveal new type of chromosome chimera

May 27, 2016

I've often wondered what happens between the time an egg is fertilized and the time the ball of cells that it becomes nestles into the uterine lining. It's a period that we know very little about, a black box of developmental ...

Shaving time to test antidotes for nerve agents

February 29, 2016

Imagine you wanted to know how much energy it took to bike up a mountain, but couldn't finish the ride to the peak yourself. So, to get the total energy required, you and a team of friends strap energy meters to your bikes ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.