Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Discovery may aid search for anti-aging drugs

Gene's action may help explain why restricting diet lengthens life in animals

A team of University of Michigan scientists has found that suppressing a newly discovered gene lengthens the lifespan of roundworms. Scientists who study aging have long known that significantly restricting food intake makes animals live longer. But the goal is to find less drastic ways to achieve the same effect in humans someday. The U-M results offer promising early evidence that scientists may succeed at finding targets for drugs that someday could allow people to live longer, healthier lives.

In a study in the August issue of Aging Cell, U-M scientists found that a gene, drr-2, is an important component in a key cellular pathway, the TOR nutrient-sensing pathway, where many scientists are looking for potential drug targets. The U-M scientists then found that when they caused the drr-2 gene to be under- or over-expressed, they could lengthen or shorten lifespan in C. elegans, a worm widely used in research. Manipulating the drr-2 gene's action produced the same effects as reducing or increasing caloric intake.

"We showed that in C. elegans, drr-2 is one of the essential genes for the TOR pathway to modulate lifespan," says Ao-Lin Allen Hsu, Ph.D., the study's senior author and a scientist at the U-M Geriatrics Center. He also is an assistant professor in internal medicine and molecular and integrative physiology at U-M. The study also found that drr-2 appears analogous to a human gene, eIF4H, that controls similar cell functions.


To find possible avenues for future anti-aging drugs, many scientists around the world are focusing on signaling pathways in cells that sense nutrients. The one Hsu examined, the target of rapamycin pathway or TOR pathway, is so named because its activity can be influenced by the drug rapamycin. Recent results from a large federal study being conducted at U-M and elsewhere have shown that in mice, rapamycin is effective at mimicking the anti-aging effects of dietary restriction.

Research in the last 25 years has shown that animals, including mammals, live longer and have lower levels of certain measures of age-related decline when scientists have restricted their food intake. No one has been able to show yet that the same effect happens in humans, though some studies are under way.

When calories or certain nutrients are restricted, scientists detect less oxidative damage in animal cells and a slower decline in DNA repair, a decline that normally occurs with age. It's thought that limiting oxidative damage and slowing the decline in DNA repair could help postpone or avoid many age-related diseases.

But scientists know relatively little about why reducing food intake causes these effects. In the last 10 years, they have made progress in identifying genes and associated proteins that are suppressed when diet is restricted. By learning more about the cell processes involved, they may be able to discover targets for future drugs that could delay aging without the need to restrict food intake.

Drugs tailored to block specific genes or proteins involved in nutrient-sensing pathways would have much more appeal than reducing what one eats. To achieve anti-aging benefits, it's thought that people would have to restrict food intake by 30 to 40 percent, a grim prospect. In addition, drugs might be designed to avoid other disadvantages of this level of dietary restriction, which include reduced fertility.

C. elegans is a tiny roundworm, a nematode whose two-week lifespan is a great advantage for scientists studying aging. The 1-millimeter-long transparent worms have other advantages, too. C. elegans exhibits many age-associated changes observed in higher organisms.

"Many genes identified in C. elegans to control the speed of aging turned out to be evolutionarily conserved, meaning that you can find them in other animals, too. And many are very similar to those found in humans," Hsu says.

Research details

Hsu and his team created different mutant strains of roundworms, some with drr-2 genes silenced and others in which the gene was over-expressed. They wanted to learn whether inactivating drr-2 is essential for TOR to influence longevity, and found that it was. Other newly discovered genes may affect TOR signaling as well. But Hsu's team has found a promising lead for anti-aging drugs of the future: They were able to show that silencing drr-2's action alone was sufficient to make worms live longer than wild-type C. elegans used as controls.

"It is known that reduction of TOR signaling in response to a change in the environment or genetic manipulation triggers a cascade of cellular signals that alter cell growth, metabolism, and protein synthesis, and decrease the pace of aging," says Hsu. "Our recent studies have shown that drr-2 might play a pivotal role in the TOR signaling network to control protein synthesis as well as longevity."

Additional U-M authors: Tsui-Ting Ching, Alisha B. Paal, Avni Mehta, and Linda Zhong, all of the Division of Geriatric Medicine, U-M Department of Internal Medicine Funding: Ellison Medical Foundation and the National Institutes of Health

Citation: DOI: 10.1111/j.1474-9726.2010.00

Anne Rueter | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>