Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecules discovered that extend life in yeast, human cells

25.08.2003


Group of compounds found in red wine, vegetables simulate benefit of low-calorie diet



Mice, rats, worms, flies, and yeast all live longer on a low-calorie diet, which also seems to protect mammals against cancer and other aging-related diseases. Now, in yeast cells, researchers at Harvard Medical School and BIOMOL Research Laboratories have for the first time found a way to duplicate the benefits of restricted calories in yeast with a group of compounds found in red wine and vegetables. One compound extended yeast life span by up to 80 percent. The molecules are also active in human cells cultured in the laboratory.

The findings are reported in the August 24 Nature advanced online edition. The research suggests a promising route to find and develop drugs to lengthen life and prevent or treat aging-related diseases.


The molecules belong to a familiar group of compounds known as polyphenols, such as the resveratrol found in red wine and the flavones found in olive oil. For these particular polyphenols, the beneficial effects seem to be independent of their famed antioxidant properties. Instead, the molecules activate sirtuins, a family of enzymes known to extend the life span of yeast and tiny lab round worms. In screening tests, the researchers found 17 molecules that stimulated SIRT1, one of seven human sirtuins, and the yeast sirtuin SIR2.

"We think sirtuins buy cells time to repair damage," said molecular biologist David Sinclair, assistant professor of pathology at Harvard Medical School and co-author of the new study. "There is a growing realization from the aging field that blocking cell death -- as long as it doesn’t lead to cancer -- extends life span."

"The sirtuin stimulation provided by certain, but not all, polyphenols may be a far more important biological effect than their antioxidant action," said co-author Konrad Howitz, director of molecular biology at BIOMOL, a biochemical reagents company in Pennsylvania.

Calorie restriction (in mammals, reducing intake to 60 or 70 percent of the normal daily calories) may be one of many mild stresses that trigger beneficial effects, a phenomenon called hormesis. To explain their new findings, the researchers propose that plant polyphenols, which increase in response to stressful conditions, cue organisms to prepare for impending harsh conditions by switching to a more beneficial survival program. They call their hypothesis "xenohormesis."

The most potent molecule in the study, resveratrol, helped yeast cells live as much as 60 to 80 percent longer, as measured by the number of generations. Other studies have linked resveratrol to health benefits in mitigating age-related diseases, including neurodegeneration, cancer and clogged arteries. In this study, researchers were surprised to find that yeast cells treated with small doses of resveratrol lived for an average of 38 generations, compared to 19 for the untreated yeast. The polyphenol worked through a known sirtuin molecular pathway to help yeast and human cells survive environmental stresses.

In experiments with human cells, resveratrol activated a similar pathway requiring SIRT1. This enabled 30 percent of the treated human cells to survive gamma radiation compared to 10 percent of untreated cells. Little is known about the human sirtuin SIRT1, except that it turns off the tumor suppressor gene p53. This raises the concern that any promotion of this pathway might promote cancer even as it switches on a longevity program. But Sinclair said that calorie-restricted animals in experiments by others have lower, not higher rates of cancer.

In the paper, the researchers report that preliminary experiments in flies and worms are encouraging. Mouse studies are in the works. They are exploring synthetic variations on the molecules, which they call sirtuin activating compounds or "STACs," to improve the sirtuin activity. They are also searching for endogenous activators that may naturally exist in human cells.

In the May 8 Nature, Sinclair’s research group reported the first known genetic link between environmental stresses and longer life in yeast. Triggered by low salt, heat, or calorie restriction (to as low as 25 percent of normal), a yeast "longevity gene" stimulated Sir2 activity. Sinclair and his colleagues are testing equivalent genes in humans to see if they similarly speed up human sirtuin activity.

The work was supported by the National Institute on Aging and the Harvard-Armenise Foundation. Researchers were further supported by fellowships and training grants from the Ellison Medical Research Foundation, the American Federation for Aging Research, the National Eye Institute, and the National Science Foundation. A provisional patent has been filed for refined versions of the natural molecules.


###
SINCLAIR BIOSKETCH

David Sinclair, PhD is an assistant professor of pathology at Harvard Medical School. His research is focused on finding small molecules and genes that can delay or prevent diseases caused by aging. His lab is one of the few in the world that studies a variety of different organisms--baker’s yeast, nematode worms, fruit flies and mice--to understand aging. In 1997, Sinclair’s research at M.I.T. identified the discovery of the cause of aging in yeast, a first for any species. This work was published in the journal Cell. In May 2003, Sinclair’s laboratory reported the discovery of a conserved "master regulatory gene" for aging in yeast that was published in the journal Nature. Sinclair’s work was featured in two books, Merchants of Immortality (S. Hall, 2003) and Timeless Quest (L. Guarente, 2003).

Dr. Sinclair received a bachelor of science with highest honors in 1991 and a PhD in Biochemistry and Molecular Genetics in 1995 from the University of New South Wales, Australia. He worked as a postdoctoral researcher with Dr. Leonard Guarente at M.I.T. for four years before joining Harvard Medical School.

Dr. Sinclair has received several awards and honors for his research, including The Thomson Prize for first place in undergraduate studies, a Helen Hay Whitney Postdoctoral Award (1996-1999), and a Special Fellowship from the Leukemia and Lymphoma Society (1999 - 2002). Sinclair was a Ludwig Scholar (2000-2002), a Harvard-Armenise Fellow (2000-2003), an American Association for Aging Research (AFAR) Fellow (2002), and is currently a New Scholar of the Ellison Medical Foundation (2001-present).

Dr. Sinclair lives in West Roxbury, Massachusetts with his wife and daughter.

John Lacey | EurekAlert!
Further information:
http://www.hms.harvard.edu/
http://www.hms.harvard.edu/news/releases/0503sinclair.html
http://www.nia.nih.gov/health/pubs/microscope/

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>