Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find new clues to biochemistry of 'anti-aging'

20.06.2006
University of Wisconsin-Madison researchers have found that sirtuins, a family of enzymes linked to a longer life span and healthier aging in humans, may orchestrate the activity of other enzymes involved in metabolic processes in the body.

Published in the June 19-23 issue of Proceedings of the National Academy of Sciences, the study is the first to show that sirtuins directly control specific metabolic enzymes - called AceCSs - in mammalian cells.

The finding, which shines a spotlight on enzymes only recently thought to play a role in the biochemistry of "anti-aging," has attracted the interest of biotechnology companies seeking to make drugs that delay the aging process and age-related diseases. The drugs could target the metabolic enzymes to produce health benefits.

"Sirtuins are very enticing because of their ability to slow the aging process," says John Denu, associate professor of biomolecular chemistry at the UW-Madison School of Medicine and Public Health (SMPH) and lead author on the study. "They also have great potential for promoting healthier aging by giving us a better understanding of - and possibly suggesting treatments for - metabolic diseases such as diabetes and neurological disorders such Alzheimer's and Huntington's diseases."

Scientists studying the genetics and physiology of sirtuins in organisms such as yeast, worms, flies and mice have shown that this enzyme family plays a role in a variety of cellular processes, including gene silencing, cell death, fatty acid metabolism, neuronal protection and life span extension.

"In humans, sirtuins have been implicated in the health benefits of calorie restriction, which is known to lengthen life span, and the enzymes are activated when they are exposed to resveratrol, a plant product found in red wine also known to extend life span," Denu says. "In addition, elevated levels of sirtuins somehow slow degeneration in nerve cells that have been damaged, and the enzymes affect aspects of metabolism responsible for controlling insulin secretion."

Denu and his team, which has published widely on sirtuins, conducted test tube studies using mouse cells to learn exactly which molecular players sirtuins act on directly. Previous studies suggested that sirtuins control genes indirectly in the cell nucleus. The first hint that sirtuins might directly control metabolic pathways came from earlier work in bacteria done by UW-Madison bacteriology professor Jorge Escalante.

The SMPH researchers found that sirtuins directly controlled the two-member class of enzymes called AceCSs (for acetyl-CoA synthetases) by activating these metabolic enzymes through the fundamental process of deacetylation. One form of sirtuin activated one type of AceCS, while another form of sirtuin activated the other AceCS. This reversible process transformed the AceCSs into a form that allows the body to utilize the small fatty acid called acetate.

"Acetate can be very important in animals as an energy source," Denu says, adding that cows and other ruminants use large quantities of it during digestion. "In humans, acetate can be obtained from the diet and as a by product of other metabolic processes. However, it is believed that we don't generally rely on it heavily as an energy source."

Denu says it's not clear what role acetate metabolism may play in the little-understood sirtuin molecular system that seems to confer so many advantages, but a connection to diabetes and aging does exist. Studies from the 1960s and early 1990s showed that diabetics and aged individuals exhibit a decreased ability to utilize acetate, he notes.

"Although the molecular links still must be established, appropriate control of our bodies' metabolic processes is essential to life extension and healthy aging," he says. "The observation that caloric restriction extends life span and appears to reduce the risk of diabetes in animal models only underscores the importance of metabolic pathways."

Denu plans to take advantage of the calorie restriction research program that has been under way for years at UW-Madison's National Primate Research Center under the direction of Richard Weindruch, SMPH professor of medicine.

Biotechnology companies are particularly intrigued by the Wisconsin team's discovery of sirtuin's direct effect on mammalian cells, in which the enzymes activate AceCS metabolic enzymes.

"This would be the easiest target, or hot spot, to aim for in developing a small molecule drug that could stimulate this process," Denu says.

Dian Land | EurekAlert!
Further information:
http://www.wisc.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

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

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>