Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers discover common cause for aging and age-related disease


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:

More articles from Health and Medicine:

nachricht Scientists develop tiny tooth-mounted sensors that can track what you eat
22.03.2018 | Tufts University

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

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: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Custom sequences for polymers using visible light

22.03.2018 | Materials Sciences

Scientists develop tiny tooth-mounted sensors that can track what you eat

22.03.2018 | Health and Medicine

Mat baits, hooks and destroys pollutants in water

22.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>