Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer drug prolongs life in flies

29.06.2015

Trametinib inhibits the same signal pathway in flies and humans and could thus conceivably also extend life expectancy in humans

Humans, yeasts and fruit flies began to evolve separately millions of years ago. Nevertheless, the cellular processes which regulate cell division and cell death – and therefore the mechanism of ageing – are similar in all of them. Scientists at the Max Planck Institute for Biology of Ageing in Cologne and University College London have now succeeded in controlling this mechanism, thus extending life expectancy in fruit flies by around twelve percent.


Older fruitfly (Drosophila melanogaster).

© Nazif Alic

They achieved this with the help of a cancer drug called Trametinib. Human cells contain the same molecular switches that Trametinib targets in fruit flies. It is therefore conceivable that the substance could be used to develop future anti-ageing drugs to extend life expectancy in humans.

To ensure a long and healthy life in humans, researchers have to understand the ageing process at the cellular level more precisely. A scientific study has now shown how Ras proteins can be manipulated to prolong the lifespans of animals.

Ras proteins play a key role in the regulation of cell processes. As molecular switches within the cellular signalling network, they control vital functions such as cell division, cell death, specialisation and metabolism. They regulate these intracellular processes via the Ras-Erk-ETS signal pathway. This network has been conserved over hundreds of millions of years of evolution and is present in single-cell organisms such as yeasts, in insects such as the fruit fly (Drosophila), as well as in mammals such as mice and humans.

It was already known that inhibition of this signal pathway can prolong the life expectancy of yeast cells. However, to achieve this, the scientists had thus far manipulated the DNA directly in order to deactivate individual genes and with them the Ras signal pathway. However, no substance was known that could slow the ageing process at this interface. Recent work by the research team has now filled this gap.

The scientists took advantage of the fact that the Ras-Erk-ETS signal pathway has been thoroughly researched in the context of cancer treatment. This is because overactivation of Ras is carcinogenic: in around a third of cancer patients, the Ras proteins of cancer cells are mutated, resulting in uncontrolled cellular division. Many cancer researchers have therefore focussed on this signal pathway - and the first drugs have already been developed to interfere with Ras signalling in order to check cancerous growth.

The researchers administered one of those substances, Trametinib, to fruit flies in the form of a food additive. Even a small dose, which is approximately equivalent to a daily dose of the drug in a human patient, increased the fruit flies’ average life expectancy by eight percent. With a moderate dose, the flies lived twelve percent longer on average.

Any drug suitable for anti-ageing applications must be effective even if it is administered during an advanced phase of life. The scientists successfully demonstrated this property. In a substudy, they administered the substance for the first time to Drosophila that were 30 days old – a ripe old age for this species. At this point, egg laying, i.e. the insects’ fertile phase, has ceased. Even when a moderate dose of the substance was given to the flies at this late point in their lifespan, it still increased their average life expectancy by seven percent. The researchers observed no adverse effects on the insects’ digestive system or food intake.

“Our findings indicate what substance classes could be used to slow the ageing process in humans,” explains Nazif Alic of University College London. “The Ras-Erk-ETS signal pathway could serve as a target for those substances.” The aim now is to investigate this pathway more closely. “The study suggests that inhibition of this signal pathway has positive effects on longevity and mortality,” says Cathy Slack, who researches at University College London and at the Max Planck Institute for Biology of Ageing. Slack emphasises that Trametinib has been approved by the FDA as a drug for the treatment of skin cancer and is therefore already in clinical use.

In mammals, Ras acts as a mediator for the insulin/IGF-1 signal pathway, which modulates life expectancy. Ras activation has effects on both the PI3/Akt and Erk/Mapk signal pathways. Until now, it was assumed that the PI3/Akt branch is primarily responsible for modulating lifespan. The findings show, however, that the Erk branch is also important in this regard. Two transcription factors controlled by Ras-Erk appear to be key mediators of these effects: Pnt, a gene expression activator, and Aop, a repressor. It therefore appears likely that life expectancy can be regulated via both branches of the signal pathway.


Contact

Prof. Dr. Linda Partridge
Max Planck Institute for Biology of Ageing, Köln
Phone: +49 221 37970-602

Email: Christine.Lesch@age.mpg.de

Scientific and Personal Assistance:
Dr. Christine Lesch


Original publication
Cathy Slack, Nazif Alic, Andrea Foley, Melissa Cabecinha, Matthew P. Hoddinott, and Linda Partridge

The Ras-Erk-ETS signalling pathway is a drug target for longevity

Cell; 25 June, 2015

Prof. Dr. Linda Partridge | Max Planck Institute for Biology of Ageing, Köln
Further information:
http://www.mpg.de/9294150/trametinib-longevity

More articles from Life Sciences:

nachricht Flavins keep a handy helper in their pocket
25.04.2018 | University of Freiburg

nachricht Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Getting electrons to move in a semiconductor

25.04.2018 | Physics and Astronomy

Reconstructing what makes us tick

25.04.2018 | Physics and Astronomy

Cheap 3-D printer can produce self-folding materials

25.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>