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 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>