Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find what type of genes affect longevity

30.06.2003


About 200 genes identified



Tracing all the genetic changes that flow from a single mutation, UCSF scientists have identified the kinds of genes and systems in the body that ultimately allow a doubling of lifespan in the roundworm, C. elegans. Humans share many of these genes, and the researchers think the new findings offer clues to increasing human youthfulness and longevity as well.

Using DNA microarray technology, the researchers found that the single life-extending mutation – a change in the gene known as daf-2 -- exerts its influence through antimicrobial and metabolic genes, through genes controlling the cellular stress response, and by dampening the activity of specific life-shortening genes.


"This study tells us that there many genes that affect lifespan, each on its own having only a small effect," said Cynthia Kenyon, PhD, UCSF professor of biochemistry and senior author on a paper in Nature reporting the research.. "The beauty of the daf-2 gene is that it can bring all of these genes together into a common regulatory circuit. This allows it to produce these enormous effects on lifespan." Kenyon is also director of the Hillblom Center for the Biology of Aging at UCSF’s Mission Bay campus.

Lead author on the paper is Coleen Murphy, PhD, a post-doctoral scientist in Kenyon’s lab.

By partially disabling one gene at a time, either in daf-2 mutants or in wild-type worms, through a technique known as RNA interference, the scientists were able to discover that no single gene by itself determines lifespan . Of the key genes, each can increase lifespan by 10 to 30 percent, the research shows. But when daf-2 engages the whole army of genes, they can produce huge changes in lifespan.

Because any individual gene appears to have a relatively small effect on lifespan, identifying the key players would have been difficult in a standard genetic screen, the scientists say, underscoring the power of DNA microarray analysis for teasing apart complex systems.

Kenyon’s team discovered ten years ago that a single mutation in the daf-2 gene, which encodes a hormone receptor similar to the human receptors for the hormones insulin and IGF-1, doubled the worms’ lifespan. The same or related hormone pathways have since been shown to affect lifespan in fruit flies and mice, and therefore are likely to control lifespan in humans as well. Her lab found that daf-2 affects lifespan through a second gene, known as daf-16, whose function was known to control the expression of other genes.

But the finding left unanswered just how longevity is achieved. What are the genes that daf-16 regulates? The new research shows that several key systems are involved. Many of the genes that affect lifespan code for antioxidant proteins, the researchers found; others code for proteins called chaperones that help repair or degrade damaged proteins. This is especially interesting, Kenyon says, because many diseases of aging involve oxidative damage or protein aggregation.

Other longevity genes found active in the long lived mutants make proteins that help ward off bacterial infections, the researchers found. Kenyon’s lab showed earlier that infections are the likely cause of death for the worm, recent research from others has shown that the long-lived animals are known to be resistant to bacterial infection. The current study shows that without these genes activated, the long-lived worms die sooner. In humans, too, infections pose a serious health problem for the aged.

"Maybe one day we will be able to tweak the insulin/IGF-1 systems in humans to produce many of the same benefits that we see in the worm," Kenyon says.

The scientists also found longevity genes affecting lipid transport and energy metabolism, as well as a host with unknown functions.

"The diversity of these lifespan gene functions is just remarkable" said Kenyon.

The long-lived worms, as well as mice with similar changes in the same genes, also are disease resistant, and the study suggests possible mechanisms for this finding. The antimicrobial response could protect against infections, and the antioxidant response can protect against diseases that involve oxidative damage. Many researchers suspect stroke and a number of neurological diseases in humans are hastened by oxidative damage.

Earlier this year, Kenyon’s lab showed in C. elegans that the damage-repairing chaperone proteins not only increase lifespan, but also delay the onset of protein-aggregation diseases similar to Huntington’s diseases.

"The marvelous thing about this new study is that it provides an explanation not only for the remarkable longevity of these animals, but also for their ability to stay healthy so long," Kenyon says.

"They just turn up the expression of many, many different genes, each of which helps out in its own way. The consequences are stunning, and if we can figure out a way to copy these effects in humans, we might all be able to live very healthy long lives," she adds.

Co-authors on the Nature paper are Cornelia Bargmann, PhD, professor of anatomy and Howard Hughes Medical Institute investigator at UCSF; Steven McCaroll, a graduate student; Hao Li, PhD, UCSF assistant professor of biochemistry; and Andrew Fraser and Ravi Kamath at the Welcome CRC Institute and Department of Genetics, University of Cambridge.


The research was supported by the National Institute on Aging and the Ellison Foundation.


Wallace Ravven | EurekAlert!
Further information:
http://www.ucsf.edu/

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>