Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover common cause for aging and age-related disease

16.05.2003


Why do serious diseases such as cancer, Alzheimer’s and Huntington’s mainly hit us in middle age or later? The links between aging and age-related diseases have proved elusive.



In studies of the powerfully informative roundworm, C. elegans, UCSF scientists have discovered that a class of molecules found in the worms and in people can both prolong life in the worm and prevent the harmful accumulation of abnormal proteins that cause a debilitating Huntington’s-like disease. The finding appears to be the first evidence in an animal of a link between aging and age-related disease.

The molecules, called "small heat-shock proteins," are known to assemble into complexes that bind to damaged or unfolded cellular proteins and prevent them from forming into harmful aggregations.


"We think we’ve found an important physiological explanation for both aging and age-related disease," said Cynthia Kenyon, PhD, the Herbert Boyer Professor of Biochemistry and Biophysics at UCSF and senior author on a paper describing the work in the May 16 issue of SCIENCE. "The question of why older people are more susceptible to so many diseases has been a fundamental, unsolved problem in biology. Our findings suggest a beautiful molecular explanation, at least for this protein-aggregation disease.

"By preventing damaged and unfolded proteins from aggregating, this one set of proteins may be able to stave off both aging and age-related disease. The small heat-shock proteins are the molecular link between the two."

The growing roster of diseases thought to be caused by protein clumping or aggregation -- Alzheimer’s, Huntington’s, Parkinson’s, prion diseases -- suggests that the small heat shock proteins may influence the onset of many age-related ailments, the researchers say. The pharmaceutical industry is already exploring ways to increase the activity of heat-shock proteins. The research by Kenyon’s laboratory indicates that if these drugs work, they may not only protect protein function, but also extend life.

Kenyon made international news 10 years ago when her laboratory showed that modifying a single gene in C. elegans doubled the worm’s healthy life-span. The gene, known as daf-2, encodes a receptor for insulin as well as for a hormone called insulin-like growth factor. The same or related pathways have since been shown to affect longevity in fruit flies and mice and are likely to control life-span in humans as well.

In neurodegenerative Huntington’s disease, brain cells produce proteins with an abnormally high number of repeating subunits called glutamine. The proteins aggregate, disrupting their function. Ultimately, people with Huntington’s disease lose control of their movements. Recently, researchers traced a similar morbid course in C. elegans, using fluorescent tags to follow the debilitating accumulation of the damaged protein. They found that in worms, as in humans, the proteins formed aggregates, but only as the animals aged.

Other researchers have shown that Kenyon’s long-lived daf-2 mutant worms accumulate the disabling proteins later in life than normal worms, so the worms have both increased life-span and delayed onset of age-related disease -- the best of both worlds.

In the new research, Kenyon’s team used DNA microarrays to find that the expression of genes for four small heat-shock proteins "sharply increased" in the long-lived daf-2 mutants.

They also found that the boost in this gene expression required two key proteins in the daf-2-insulin/IGF-1 receptor pathway -- the proteins DAF-16 and HSF-1, both "transcription factors" that direct gene activity. The involvement of HSF-1 in the daf-2 pathway had not been known.

To determine if the small heat-shock proteins influenced life-span, the scientists used a fairly new technique called RNA interference, or RNAi, to partially disable the small heat-shock protein genes. They showed that the heat-shock proteins account for a substantial part of the worms’ increased life-span.

(In a related study, researchers at the Buck Institute for Aging led by Gordon Lithgow have recently shown that raising the levels of small heat-shock proteins can extend the lifespan of C. elegans.)

Small heat-shock proteins are known to inhibit protein aggregation, so Kenyon and her colleagues used the powerful RNAi technique to show that decreased heat-shock protein gene expression accelerated the onset of Huntington’s-like "polyglutamine" protein aggregation -- strong evidence that small heat shock proteins normally delay the harmful protein aggregation.

Small heat-shock proteins, they conclude, may influence the rates of aging and of polyglutatmine aggregation "coordinately." Mutations in the DAF-2 pathway, they write, may delay both aging and susceptibility to this age-related disease, at least in part by increasing small heat-shock protein gene expression.

"The small heat-shock proteins appear to be the link between aging and at least this age-related disease," Kenyon stresses. "And by regulating the small heat-shock proteins, the insulin/IGF-1 pathway can influence both aging and age-related disease coordinately."

Kenyon, who was elected this month to the National Academy of Sciences, directs UCSF’s Hillblom Center for the Biology of Aging at the University’s new Mission Bay campus.


Lead author on the SCIENCE paper is Ao-Lin Hsu, PhD; co-author is Coleen T. Murphy. Both are post-doctoral scientists in Kenyon’s lab.

The research was funded by the Ellison Foundation and the National Institute of Aging.

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

More articles from Health and Medicine:

nachricht How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Optical Nanoscope Allows Imaging of Quantum Dots

Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.

Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Researchers reveal how microbes cope in phosphorus-deficient tropical soil

23.01.2018 | Earth Sciences

Opening the cavity floodgates

23.01.2018 | Life Sciences

Siberian scientists suggested a new method for synthesizing a promising magnetic material

23.01.2018 | Materials Sciences

VideoLinks Science & Research
Overview of more VideoLinks >>>