Starvation hormone markedly extends mouse life span, researchers show

October 16, 2012
Drs. David Mangelsdorf, Yuan Zhang, and Steven Kliewer (l-r) have demonstrated that a starvation hormone markedly extends life span in mice without the need for calorie restriction. Credit: UT Southwestern Medical Center

A study by UT Southwestern Medical Center researchers finds that a starvation hormone markedly extends life span in mice without the need for calorie restriction.

"Restricting has been shown to extend lifespan in several different kinds of animals. In our study, we found that produced more of the fibroblast growth factor-21 (FGF21) got the benefits of dieting without having to limit their food intake. Male mice that overproduced the hormone had about a 30 percent increase in average and had about a 40 percent increase in average life span," said senior author Dr. Steven Kliewer, professor of and pharmacology.

The study published online in eLife – a new peer-reviewed, open access journal – defined average life span as the point at which half the members of a given test group remained alive. A study to determine differences in maximum life span is ongoing: While none of the untreated mice lived longer than about 3 years, some of the female mice that overproduced FGF21 were still alive at nearly 4 years, the researchers report.

FGF21 seems to provide its health benefits by increasing and blocking the growth hormone/insulin-like growth factor-1 signaling pathway. When too abundant, growth hormone can contribute to , cancer, and other diseases, the researchers said.

FGF21 is a hormone secreted by the liver during fasting that helps the body adapt to starvation. It is one of three growth factors that are considered atypical because they behave like hormones, which are substances created by one part of the body that have effects in other parts, the researchers said.

"Prolonged overproduction of the hormone FGF21 causes mice to live extraordinary long lives without requiring a decrease in food intake. It mimics the health benefits of dieting without having to diet," said co-author Dr. David Mangelsdorf, chairman of pharmacology and a Howard Hughes Medical Institute (HHMI) investigator at UT Southwestern.

"Aging and aging-related diseases represent an increasing burden on modern society. Drugs that slow the aging process would be very desirable. These findings raise the possibility of a hormone therapy to extend life span," said Dr. Mangelsdorf, who runs a research laboratory with Dr. Kliewer. They first identified FGF21's starvation-fighting effects in a 2007 study.

Lead author Dr. Yuan Zhang, an instructor of pharmacology, said the study was considered risky because all involved understood it would be at least two years – an average mouse life span – before there would be any evidence of whether elevated production of FGF21 would affect longevity.

Previous research has found that FGF21 can reduce weight in obese mice. The mice that overproduced FGF21 in this latest study were lean throughout their lives and remained lean even while eating slightly more than the wild-type mice, the researchers said.

The hormone does have some downsides: FGF21 overproducers tended to be smaller than wild-type mice and the female mice were infertile. While FGF21 overproducers had significantly lower bone density than wild-type mice, the FGF21-abundant exhibited no ill effects from the reduced bone density and remained active into old age without any broken bones, the researchers said.

"FGF21 is not affecting their mobility. These guys are spry. They live nice, long lives," Dr. Kliewer said. "But the decreased bone density and female infertility will require additional research to determine if it is possible to separate out the hormone's life span-extending effects from its effect on bone," he added.

Explore further: Study: Rapid bone loss as possible side effect of anti-obesity drug now in clinical trials

Related Stories

Study: Rapid bone loss as possible side effect of anti-obesity drug now in clinical trials

February 7, 2012
An endocrine hormone used in clinical trials as an anti-obesity and anti-diabetes drug causes significant and rapid bone loss in mice, raising concerns about its safe use, UT Southwestern Medical Center researchers have shown.

Antibody injection promising for diabetes and obesity

December 16, 2011
(Medical Xpress) -- Researchers at Genetech Inc. in South San Francisco, California, led by molecular biologist Junichiro Sonoda, have discovered that a single injection of antibodies into obese diabetic mice provided a marked ...

Recommended for you

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

Age and gut bacteria contribute to multiple sclerosis disease progression

November 17, 2017
Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to multiple sclerosis (MS) disease onset and progression.

Molecular guardian defends cells, organs against excess cholesterol

November 16, 2017
A team of researchers at the Harvard T. H. Chan School of Public Health has illuminated a critical player in cholesterol metabolism that acts as a molecular guardian in cells to help maintain cholesterol levels within a safe, ...

Prototype ear plug sensor could improve monitoring of vital signs

November 16, 2017
Scientists have developed a sensor that fits in the ear, with the aim of monitoring the heart, brain and lungs functions for health and fitness.

Ancient enzyme could boost power of liquid biopsies to detect and profile cancers

November 16, 2017
Scientists are developing a set of medical tests called liquid biopsies that can rapidly detect the presence of cancers, infectious diseases and other conditions from only a small blood sample. Researchers at The University ...

FDA to crack down on risky stem cell offerings

November 16, 2017
U.S. health authorities announced plans Thursday to crack down on doctors pushing stem cell procedures that pose the gravest risks to patients amid an effort to police a burgeoning medical field that previously has received ...

0 comments

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.