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 Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

Quantum optical sensor for the first time tested in space – with a laser system from Berlin

23.01.2017 | Physics and Astronomy

The interactome of infected neural cells reveals new therapeutic targets for Zika

23.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>