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 Solving the efficiency of Gram-negative bacteria
22.03.2019 | Harvard University

nachricht Bacteria bide their time when antibiotics attack
22.03.2019 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>